WO2025111269A1

WO2025111269A1 - N-acetyl muramic acid derived positron emission tomography tracers for imaging infection

Info

Publication number: WO2025111269A1
Application number: PCT/US2024/056529
Authority: WO
Inventors: David M. Wilson; Sanghee Lee
Original assignee: University of California Berkeley; University of California San Diego UCSD
Current assignee: University of California Berkeley; University of California San Diego UCSD
Priority date: 2023-11-20
Filing date: 2024-11-19
Publication date: 2025-05-30
Anticipated expiration: 2026-05-20

Abstract

The present disclosure relates generally to compounds, compositions, and methods for detecting bacteria, including gram-positive bacteria such as S. aureus, in a subject.

Description

Attorney Docket: 048536-772001WO N-ACETYL MURAMIC ACID DERIVED POSITRON EMISSION TOMOGRAPHY TRACERS FOR IMAGING INFECTION _{[0001] The present application claims priority under 35 U.S.C. § 119(e) to U.S. Provisional} Patent Application Number 63/601,002 titled “N-ACETYL MURAMIC ACID DERIVED POSITRON EMISSION TOMOGRAPHY TRACERS FOR IMAGING INFECTION”, filed on November 20, 2023, the entire contents of which is hereby expressly incorporated by reference herein. STATEMENT AS TO RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSORED RESEARCH AND DEVELOPMENT _{[0002] This application was made with government support under grants R01EB024014 and} R01EB030897, awarded by the National Institutes of Health. The government has certain rights to the invention. FIELD _{[0003] The present disclosure relates generally to compositions and methods for detecting} bacteria in a subject, including gram-positive bacteria such as S. aureus. BACKGROUND _{[0004] Patients with symptoms of infection are frequently prescribed antibiotics when they do} not have a bacterial cause, leading to over-prescription of these therapies. In the hospital setting, infections are frequently poorly localized and would benefit from a bacteria-specific imaging approach. Finally, for physicians that treat infectious diseases, is frequently difficult to determine proper antibiotic response, especially in the setting of prosthetic implants. An imaging approach that targets bacteria themselves, rather than the host response (detected by physical exam or routine CT, MR and nuclear imaging) would be a major advance in patient treatment. _{[0005] Several imaging methods have been developed that explicitly target bacteria-specific} metabolic pathways, using clinically translatable technologies such as positron emission tomography (PET) or magnetic resonance imaging (MRI). Some promising PET radiotracers include radiolabeled sugars and sugar alcohols that are not efficiently metabolized by humans, such as 2-deoxy-2-[¹⁸F]fluoro-D-sorbitol ([¹⁸F]FDS)(Weinstein, E. A., et al., Sci. Transl. Med. Attorney Docket: 048536-772001WO _{2014, 6, 259; Ordonez, A. A. et al., Sci. Transl. Med. 2021, 13, 589). These methods show} clinical potential, but many are limited in detecting gram-positive organisms including Staphylococcus aureus. For example, [¹⁸F]FDS accumulates in gram-negative Enterobacteriaceae only. This selectivity represents a limitation for detecting infections caused by other bacteria. _{[0006] D-amino acid-derived tracers have been studied (Neumann, K. D. et al., Sci. Rep.} 2017, 7, 7903; Stewart, M. N. et al., ACS Infect. Dis.2020, 6, 43–49; Polvoy, I. et al., Eur. J. Nucl. Med. Mol. Imaging 2022, 49, 3761–3771) and D-[3-¹¹C]alanine (Parker, M. F et al., ACS Cent. Sci.2020, 6, 155–165) (see FIG.1, FIG.2). A major limitation of these D-amino acid- derived tracers is the short half-life of carbon-11 (20 minutes), which limits their application in the acute care setting (i.e. emergency room, hospital) based on the need for an on-site cyclotron and difficult logistics related to radiosynthesis, quality control, patient transport and technologist use. However, many acutely ill patients are treated at facilities lacking a cyclotron. _{[0007] There is a need for bacteria-specific tracers with (1) a longer half-life, (2) a} straightforward radio-synthesis, and (3) sensitivity to gram-positive organisms including S. aureus. SUMMARY _{[0008] This section provides a general summary of the disclosure and is not comprehensive of} its full scope or all its features. _{[0009] In one aspect, provided is a compound having the structure of Formula (I)} , or a pharmaceutically acceptable R¹ is ¹⁸F;

R² is H, D, ¹⁹F, or unsubstituted C1-C5 alkyl; R³ is H, D, ¹⁹F, or unsubstituted C1-C5 alkyl; and R^x is H, methyl, or ethyl. Attorney Docket: 048536-772001WO In embodiments, the compound has the structure of Formula (Ia) , or a pharmaceutically acceptable

_{[0010] In another aspect, provided is a compound having the structure of Formula (II)} ,

or a pharmaceutically acceptable salt thereof, wherein: R¹ is ¹⁸F; R² is H, D, ¹⁹F, or unsubstituted C1-C5 alkyl; R³ is H, D, ¹⁹F, or unsubstituted C1-C5 alkyl; and R^x is H, methyl, or ethyl. In embodiments, the compound has the structure of Formula (IIa) , or a pharmaceutically _{[0011] In another aspect,}

_{structure of Formula (III)} Attorney Docket: 048536-772001WO ,

or a pharmaceutically R¹ is ¹⁸F; and R^x is H, methyl, or ethyl. In embodiments, the compound has the structure of Formula (IIIa) , or a pharmaceutically

_{[0012] In another aspect, provided is a compound having the structure of Formula (IV)} , or a pharmaceutically 1¹

R is ⁸F; and R^x is H, methyl, or ethyl. _{[0013] In another aspect, provided are pharmaceutical compositions including a compound} disclosed herein, such as a compound of Formula (I), (Ia), (II), or (IIa), or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient. _{[0014] In another aspect, provided are methods of detecting a bacteria in a subject, including} (i) administering an effective amount of an imaging agent including an ¹⁸F label to the subject; Attorney Docket: 048536-772001WO (ii) allowing the bacteria in the subject to incorporate the ¹⁸F label intracellularly or into the bacterial cell wall of the bacteria, thereby forming ¹⁸F labeled bacteria; and (iii) detecting the ¹⁸F label, thereby detecting the bacteria in the subject, wherein the imaging agent including an ¹⁸F label is a compound as described herein, or a pharmaceutically acceptable salt thereof, such as a compound of Formula (I), (Ia), (II), or (IIa). _{[0015] In another aspect, provided are methods of detecting a bacteria in a subject, including} (i) administering an effective amount of an imaging agent including an ¹⁸F label to the subject; (ii) allowing the bacteria in the subject to incorporate the ¹⁸F label intracellularly or into the bacterial cell wall of the bacteria, thereby forming an ¹⁸F labeled bacteria; and (iii) detecting the ¹⁸F labeled bacteria in the subject, wherein the imaging agent including an ¹⁸F label is a compound as described herein, or a pharmaceutically acceptable salt thereof, such as a compound of Formula (I), (Ia), (II), or (IIa). _{[0016] In another aspect, provided are methods of detecting a bacteria in a subject, including} (i) administering an effective amount of an imaging agent including an ¹⁸F label to the subject; (ii) allowing the bacteria in the subject to incorporate the ¹⁸F label intracellularly, into the bacterial cell wall, or into the periplasmic space of the bacteria, thereby forming ¹⁸F labeled bacteria; and (iii) detecting the ¹⁸F label, thereby detecting the bacteria in the subject, wherein the imaging agent including an ¹⁸F label is a compound as described herein, or a pharmaceutically acceptable salt thereof, such as a compound of Formula (I), (Ia), (II), or (IIa). _{[0017] In another aspect, provided are methods of detecting a bacteria in a subject, including} (i) administering an effective amount of an imaging agent including an ¹⁸F label to the subject; (ii) allowing the bacteria in the subject to incorporate the ¹⁸F label intracellularly, into the bacterial cell wall, or into the periplasmic space of the bacteria, thereby forming an ¹⁸F labeled bacteria; and (iii) detecting the ¹⁸F labeled bacteria in the subject, wherein the imaging agent including an ¹⁸F label is a compound as described herein, or a pharmaceutically acceptable salt thereof, such as a compound of Formula (I), (Ia), (II), or (IIa). Attorney Docket: 048536-772001WO _{[0018] In embodiments, the methods further include:} (v) administering a therapeutic agent to the subject; (vi) allowing the bacteria in the subject to respond to the therapeutic agent; and (vii) monitoring the therapeutic effect of the therapeutic agent. _{[0019] In embodiments, the methods further include:} (iv) selecting a therapeutic agent for treating the bacteria in the subject; (v) administering the therapeutic agent to the subject; (vi) allowing the bacteria in the subject to respond to the therapeutic agent; and (vii) monitoring the therapeutic effect of the therapeutic agent. _{[0020] In some embodiments, monitoring the therapeutic effect of the therapeutic agent} includes (vii-1) administering an effective amount of the imaging agent including an ¹⁸F label to the subject; (vii-2) allowing the bacteria in the subject to incorporate the ¹⁸F label intracellularly or into the bacterial cell wall of the bacteria, thereby forming ¹⁸F labeled bacteria; (vii-3) detecting the ¹⁸F label, thereby detecting the bacteria in the subject; and (vii-4) identifying a change from the detection from step (iii) to the detection from step (vii-3). _{[0021] In some embodiments, monitoring the therapeutic effect of the therapeutic agent} includes (vii-1) administering an effective amount of the imaging agent including an ¹⁸F label to the subject; (vii-2) allowing the bacteria in the subject to incorporate the ¹⁸F label intracellularly, into the bacterial cell wall, or into the periplasmic space of the bacteria, thereby forming ¹⁸F labeled bacteria; (vii-3) detecting the ¹⁸F label, thereby detecting the bacteria in the subject; and (vii-4) identifying a change from the detection from step (iii) to the detection from step (vii-3). _{[0022] In some embodiments, monitoring the therapeutic effect of the therapeutic agent} includes Attorney Docket: 048536-772001WO (vii-1) administering an effective amount of the imaging agent including an ¹⁸F label to the subject; (vii-2) allowing the bacteria in the subject to incorporate the ¹⁸F label intracellularly or into the bacterial cell wall of the bacteria, thereby forming ¹⁸F labeled bacteria; (vii-3) detecting the ¹⁸F labeled bacteria in the subject; and (vii-4) identifying a change from the detection from step (iii) to the detection from step (vii-3). _{[0023] In some embodiments, monitoring the therapeutic effect of the therapeutic agent} includes (vii-1) administering an effective amount of the imaging agent including an ¹⁸F label to the subject; (vii-2) allowing the bacteria in the subject to incorporate the ¹⁸F label intracellularly, into the bacterial cell wall, or into the periplasmic space of the bacteria, thereby forming ¹⁸F labeled bacteria; (vii-3) detecting the ¹⁸F labeled bacteria in the subject; and (vii-4) identifying a change from the detection from step (iii) to the detection from step (vii-3). _{[0024] The foregoing summary is illustrative only and is not intended to be in any way} limiting. In addition to the illustrative embodiments and features described herein, further aspects, embodiments, objects and features of the disclosure will become fully apparent from the drawings and the detailed description and the claims. BRIEF DESCRIPTION OF THE DRAWINGS _{[0025] FIG. 1 shows a depiction of the bacterial cell wall.} _{[0026] FIG. 2 shows an example of a chemical structure of a peptidoglycan monomer (PGM)} consisting of N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM) with a pentapeptide (L-Ala, D-Glu, L-Lys, D-Ala-D-Ala); D-amino acid-derived [¹¹C]-tracers; and [¹⁸F]FMA, an exemplary ¹⁸F-labeled N-acetylmuramic acid tracer of the instant disclosure. _{[0027] FIG. 3 shows semi-preparative HPLC profile of a crude mixture of (R,S)-[18F]FMA} prepared as described in Example 1. Attorney Docket: 048536-772001WO _{[0028] FIG. 4 shows time-dependent α-β interconversion of (S)-[18F]FMA after HPLC} purification (0, 30, 60, 120, and 240 min) at ambient conditions, monitored by analytical HPLC. _{[0029] FIG. 5 shows time-dependent α-β interconversion of (R)-[18F]FMA after HPLC} purification (0, 30, 60, 120, and 240 min) at ambient conditions, monitored by analytical HPLC. _{[0030] FIG. 6 shows in vitro cellular uptake of (S)-[18F]FMA and (R)-[18F]FMA in S. aureus.} H.K.: heat-killed, Block: blocked with N-acetyl muramic acid (0.1 mM). *P<0.05, **P<0.01, ***P<0.001, n.s.: not significant. _{[0031] FIG. 7 shows in vitro cellular uptake of (S)-[18F]FMA and (R)-[18F]FMA in E. coli.} H.K.: heat-killed, Block: blocked with N-acetyl muramic acid (0.1 mM). *P<0.05, **P<0.01, ***P<0.001, n.s.: not significant. _{[0032] FIG. 8 shows sensitivity analysis of (S)-[18F]FMA and (R)-[18F]FMA in different} bacterial pathogens. *P<0.05, **P<0.01, ***P<0.001, n.s.: not significant. _{[0033] FIG. 9 shows a representative time-course PET/CT imaging of (S)-[18F]FMA in a} normal mouse. _{[0034] FIG. 10 shows time-activity curves of (S)-[18F]FMA in organs of normal mice.} _{[0035] FIG. 11 shows PET/CT imaging protocol of (S)-[18F]FMA in normal and infected} mice. _{[0036] FIG. 12 shows Representative PET/CT images of (S)-[18F]FMA in mice 90 min post-} injection. _{[0037] FIG. 13 shows PET ROI-derived SUV ratio (live vs H.K.) and Ex vivo %IDg-1 ratio} (live vs H.K.) for (S)-[¹⁸F]FMA in normal and infected mice. n.s.: not significant, **P<0.01, ***P<0.001. _{[0038] FIG. 14 shows time-activity curves of (S)-[18F]FMA in live (left muscle, black circle)} and heat-killed (right muscle, white circle) in normal and infected mice. _{[0039] FIG. 15 shows representative PET/CT images of (R)-[18F]FMA in mice 90 min post-} injection. _{[0040] FIG. 16 shows PET ROI-derived SUV ratio (live vs H.K.) and Ex vivo %IDg-1 ratio} (live vs H.K.) for (R)-[¹⁸F]FMA in normal and infected mice (murine myositis model). n.s.: not significant, *P<0.05, **P<0.01, ***P<0.001. _{[0041] FIG. 17 shows time-activity curves of (R)-[18F]FMA in live (left muscle, black circle)} and heat-killed (right muscle, white circle) in normal and infected mice Attorney Docket: 048536-772001WO _{[0042] FIG. 18 shows representative microPET/CT images of (R)-[18F]FMA in mice 90 min} post-injection. Cohorts of mice (n=4) inoculated with 10⁴, 10⁵, 10⁶ CFUs of S. aureus in the left muscle (white dash circle) and 10-fold higher concentration of corresponding heat-killed in the right muscle (red dahs circle), respectively. _{[0043] FIG. 19 shows microPET ROI-derived SUV ratio (live vs H.K.) and ex vivo %IDg-1} ratio (live vs H.K.) for (R)-[¹⁸F]FMA in healthy and infected mice. _{[0044] In the following detailed description, reference is made to the Figures, which form a} part hereof. The illustrative alternatives described in the detailed description, drawings, and claims are not meant to be limiting. Other alternatives may be used and other changes may be made without departing from the spirit or scope of the subject matter presented here. It will be readily understood that the aspects, as generally described herein, and illustrated in the Figures, can be arranged, substituted, combined, and designed in a wide variety of different configurations, all of which are explicitly contemplated and make part of this application. DETAILED DESCRIPTION OF THE DISCLOSURE _{[0045] In general, the present disclosure relates, inter alia, to compositions and methods for} infection imaging using an amino sugar component of peptidoglycan, namely derivatives of N- acetyl muramic acid (NAM) labeled with the longer-lived fluorine-18 (t_1/2 = 109.6 min) radioisotope. _{[0046] Although various features of the disclosures may be described in the context of a} single embodiment, the features may also be provided separately or in any suitable combination. Conversely, although the disclosures may be described herein in the context of separate embodiments for clarity, the disclosures may also be implemented in a single embodiment. Any published patent applications and any other published references, documents, manuscripts, and scientific literature cited herein are incorporated herein by reference for any purpose. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting. _{[0047] In the following detailed description, reference is made to the accompanying drawings,} which form a part hereof. In the drawings, similar symbols generally identify similar components, unless context dictates otherwise. The illustrative alternatives described in the detailed description, drawings, and claims are not meant to be limiting. Other alternatives may Attorney Docket: 048536-772001WO be used and other changes may be made without departing from the spirit or scope of the subject matter presented here. It will be readily understood that the aspects, as generally described herein, and illustrated in the Figures, can be arranged, substituted, combined, and designed in a wide variety of different configurations, all of which are explicitly contemplated and make part of this application. D^EFINITIONS _{[0048] Unless otherwise defined, all terms of art, notations, and other scientific terms or} terminology used herein are intended to have the meanings commonly understood by those of skill in the art to which this application pertains. In some cases, terms with commonly understood meanings are defined herein for clarity and/or for ready reference, and the inclusion of such definitions herein should not necessarily be construed to represent a substantial difference over what is generally understood in the art. Many of the techniques and procedures described or referenced herein are well understood and commonly employed using conventional methodology by those skilled in the art. _{[0049] The singular form “a”, “an”, and “the” include plural references unless the context} clearly dictates otherwise. For example, the term “a cell” includes one or more cells, including mixtures thereof. “A and/or B” is used herein to include all of the following alternatives: “A”, “B”, “A or B”, and “A and B.” _{[0050] The terms “administration” and “administering”, as used herein, refer to the delivery} of a compound, composition or formulation by an administration route including, but not limited to, oral, intravenous, intra-arterial, intramuscular, intraperitoneal, subcutaneous, intramuscular, and topical administration, or combinations thereof. The term includes, but is not limited to, administering by a medical professional and self-administering. _{[0051] As used herein, a “subject” or an “individual” includes animals, such as human (e.g.,} human individuals) and non-human animals. In embodiments, a “subject” or “individual” is an individual under the care of a physician. Thus, the subject can be a human individual or an individual who has, is at risk of having, or is suspected of having a disease of interest (e.g., cancer) and/or one or more symptoms of the disease. The subject can also be an individual who is diagnosed with a risk of the condition of interest at the time of diagnosis or later. The term “non-human animals” includes all vertebrates, e.g., mammals, e.g., rodents, e.g., mice, and non- Attorney Docket: 048536-772001WO mammals, such as non-human primates, e.g., sheep, dogs, cows, chickens, amphibians, reptiles, and the like. _{[0052] The term “alkyl” by itself or as part of another substituent, means, unless otherwise} stated, a straight (i.e., unbranched) or branched carbon chain (or carbon), or combination thereof, which may be fully saturated, mono- or polyunsaturated and can include mono-, di- and multivalent radicals. The alkyl may include a designated number of carbons (e.g., C1-C10 means one to ten carbons). Alkyl is an uncyclized chain. Examples of saturated hydrocarbon radicals include, but are not limited to, groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, t- butyl, isobutyl, sec-butyl, methyl, homologs and isomers of, for example, n-pentyl, n-hexyl, n- heptyl, n-octyl, and the like. An unsaturated alkyl group is one having one or more double bonds or triple bonds. Examples of unsaturated alkyl groups include, but are not limited to, vinyl, 2-propenyl, crotyl, 2-isopentenyl, 2-(butadienyl), 2,4-pentadienyl, 3-(1,4-pentadienyl), ethynyl, 1- and 3-propynyl, 3-butynyl, and the higher homologs and isomers. An alkoxy is an alkyl attached to the remainder of the molecule via an oxygen linker (-O-). An alkyl moiety may be an alkenyl moiety. An alkyl moiety may be an alkynyl moiety. An alkyl moiety may be fully saturated. An alkenyl may include more than one double bond and/or one or more triple bonds in addition to the one or more double bonds. An alkynyl may include more than one triple bond and/or one or more double bonds in addition to the one or more triple bonds. _{[0053] An “imaging agent” as used herein is a composition, substance, element, or} compound; or moiety thereof; which is administered to a subject and is detectable by appropriate means such as via positron emission tomography (PET). _{[0054] An “18F label” as used herein is an 18F radionuclide. The 18F label may be included in} an imaging agent, e.g. covalently bonded to the remainder of the structure of the imaging agent. The ¹⁸F label may be included in an imaging agent and administered to a subject. After administration to a subject, the ¹⁸F label may be included in tissues or cells, e.g. intracellularly within bacteria (e.g., within the cytoplasm or the periplasmic space), or incorporated into the bacterial cell wall. After administration to a subject, the ¹⁸F label may be included in tissues or cells, e.g. intracellularly within bacteria, incorporated into the bacterial cell wall, or into the periplasmic space of the bacteria. _{[0055] A “PET scan” as used herein is a method of detecting a radioactive signal, e.g. from a} positron-emitting radionuclide such as ¹⁸F, or a compound, composition, or other moiety that Attorney Docket: 048536-772001WO includes the positron-emitting radionuclide. As used herein, a “PET scan” includes combination methods such as a PET-CT scan or a PET-MR scan. A PET scan (or PET-CT or PET-MR scan) may be used to generate a PET image which may be two-dimensional or three- dimensional. _{[0056] As used herein, the term “salt” refers to acid or base salts of the compounds used in} the methods of the present invention. Illustrative examples of acceptable salts are mineral acid (hydrochloric acid, hydrobromic acid, phosphoric acid, and the like) salts, organic acid (acetic acid, propionic acid, glutamic acid, citric acid and the like) salts, quaternary ammonium (methyl iodide, ethyl iodide, and the like) salts. _{[0057] The term “pharmaceutically acceptable salts” is meant to include salts of the active} compounds that are prepared with relatively nontoxic acids or bases, depending on the particular substituents found on the compounds described herein. When compounds of the present disclosure contain relatively acidic functionalities, base addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of the desired base, either neat or in a suitable inert solvent. Examples of pharmaceutically acceptable base addition salts include sodium, potassium, calcium, ammonium, organic amino, or magnesium salt, or a similar salt. When compounds of the present disclosure contain relatively basic functionalities, acid addition salts can be obtained by contacting the neutral form of such compounds with a sufficient amount of the desired acid, either neat or in a suitable inert solvent. Examples of pharmaceutically acceptable acid addition salts include those derived from inorganic acids like hydrochloric, hydrobromic, nitric, carbonic, monohydrogencarbonic, phosphoric, monohydrogenphosphoric, dihydrogenphosphoric, sulfuric, monohydrogensulfuric, hydriodic, or phosphorous acids and the like, as well as the salts derived from relatively nontoxic organic acids like acetic, propionic, isobutyric, maleic, malonic, benzoic, succinic, suberic, fumaric, lactic, mandelic, phthalic, benzenesulfonic, p-tolylsulfonic, citric, tartaric, oxalic, methanesulfonic, and the like. Also included are salts of amino acids such as arginate and the like, and salts of organic acids like glucuronic or galactunoric acids and the like (see, for example, Berge et al., “Pharmaceutical Salts”, Journal of Pharmaceutical Science, 1977, 66, 1- 19). Certain specific compounds of the present disclosure contain both basic and acidic functionalities that allow the compounds to be converted into either base or acid addition salts. Attorney Docket: 048536-772001WO [0001] Thus, the compounds of the present disclosure may exist as salts, such as with pharmaceutically acceptable acids. The present disclosure includes such salts. Non-limiting examples of such salts include hydrochlorides, hydrobromides, phosphates, sulfates, methanesulfonates, nitrates, maleates, acetates, citrates, fumarates, propionate, tartrates (e.g., (+)-tartrates, (-)-tartrates, or mixtures thereof including racemic mixtures), succinates, benzoates, and salts with amino acids such as glutamic acid, and quaternary ammonium salts (e.g. methyl iodide, ethyl iodide, and the like). These salts may be prepared by methods known to those skilled in the art. [0002] The neutral forms of the compounds are preferably regenerated by contacting the salt with a base or acid and isolating the parent compound in the conventional manner. The parent form of the compound may differ from the various salt forms in certain physical properties, such as solubility in polar solvents. _{[0058] A “therapeutic agent” as used herein refers to an agent (e.g., compound or composition} described herein) that when administered to a subject will have the intended effect, e.g., treatment or amelioration of an injury, disease, pathology or condition, or their symptoms including any objective or subjective parameter of treatment such as abatement; remission; diminishing of symptoms or making the injury, pathology or condition more tolerable to the patient; slowing in the rate of degeneration or decline; making the final point of degeneration less debilitating; or improving a patient’s physical or mental well-being. _{[0059] A “therapeutic effect” refers to an intended effect e.g., treatment or amelioration of an} injury, disease, pathology or condition, or their symptoms including any objective or subjective parameter of treatment such as abatement; remission; diminishing of symptoms or making the injury, pathology or condition more tolerable to the patient; slowing in the rate of degeneration or decline; making the final point of degeneration less debilitating; or improving a patient’s physical or mental well-being. A therapeutic effect as described herein includes elimination of or reduction in the severity of a bacterial infection, e.g. a reduction in the bacterial load, a reduction in the size of the tissue regions in which the bacteria are localized, and/or reduction in symptoms associated with the infection. _{[0060] An “effective amount” is an amount sufficient for a compound to accomplish a stated} purpose relative to the absence of the compound (e.g. achieve the effect for which it is administered, treat a disease, reduce enzyme activity, increase enzyme activity, reduce a Attorney Docket: 048536-772001WO signaling pathway, or reduce one or more symptoms of a disease or condition). An example of an “effective amount” of an imaging agent as described herein is an amount sufficient to contribute to the detection as described herein, e.g. the detection of bacteria. An example of an “effective amount” of a therapeutic agent is an amount sufficient to contribute to the treatment, prevention, or reduction of a symptom or symptoms of a disease, which could also be referred to as a “therapeutically effective amount.” A “reduction” of a symptom or symptoms (and grammatical equivalents of this phrase) means decreasing of the severity or frequency of the symptom(s), or elimination of the symptom(s). The exact amounts will depend on the purpose of the treatment, and will be ascertainable by one skilled in the art using known techniques (see, e.g., Lieberman, Pharmaceutical Dosage Forms (vols.1-3, 1992); Lloyd, The Art, Science and Technology of Pharmaceutical Compounding (1999); Pickar, Dosage Calculations (1999); and Remington: The Science and Practice of Pharmacy, 20th Edition, 2003, Gennaro, Ed., Lippincott, Williams & Wilkins). _{[0061] Where a range of values is provided, it is understood that each intervening value, to} the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limit of that range and any other stated or intervening value in that stated range, is encompassed within the disclosure. The upper and lower limits of these smaller ranges may independently be included in the smaller ranges, and are also encompassed within the disclosure, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the disclosure. _{[0062] Certain ranges are presented herein with numerical values being preceded by the term} “about.” The term “about” is used herein to provide literal support for the exact number that it precedes, as well as a number that is near to or approximately the number that the term precedes. In determining whether a number is near to or approximately a specifically recited number, the near or approximating unrecited number may be a number which, in the context in which it is presented, provides the substantial equivalent of the specifically recited number. _{[0063] As will be understood by one having ordinary skill in the art, for any and all purposes,} such as in terms of providing a written description, all ranges disclosed herein also encompass any and all possible sub-ranges and combinations of sub-ranges thereof. Any listed range can be easily recognized as sufficiently describing and enabling the same range being broken down Attorney Docket: 048536-772001WO into at least equal halves, thirds, quarters, fifths, tenths, etc. As a non-limiting example, each range discussed herein can be readily broken down into a lower third, middle third and upper third, etc. As will also be understood by one skilled in the art all language such as “up to,” “at least,” “greater than,” “less than,” and the like include the number recited and refer to ranges which can be subsequently broken down into sub-ranges as discussed above. Finally, as will be understood by one skilled in the art, a range includes each individual member. Thus, for example, a group having 1-3 articles refers to groups having 1, 2, or 3 articles. Similarly, a group having 1-5 articles refers to groups having 1, 2, 3, 4, or 5 articles, and so forth. _{[0064] It is understood that aspects and embodiments of the disclosure described herein} include “comprising,” “consisting,” and “consisting essentially of” aspects and embodiments. As used herein, “comprising” is synonymous with “including,” “containing,” or “characterized by,” and is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. As used herein, “consisting of” excludes any elements, steps, or ingredients not specified in the claimed composition or method. As used herein, “consisting essentially of” does not exclude materials or steps that do not materially affect the basic and novel characteristics of the claimed composition or method. Any recitation herein of the term “comprising”, particularly in a description of components of a composition or in a description of steps of a method, is understood to encompass those compositions and methods consisting essentially of and consisting of the recited components or step. _{[0065] Headings, e.g., (a), (b), (i) etc., are presented merely for ease of reading the} specification and claims. The use of headings in the specification or claims does not require the steps or elements be performed in alphabetical or numerical order or the order in which they are presented. _{[0066] It is appreciated that certain features of the disclosure, which are, for clarity, described} in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the disclosure, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable sub- combination. All combinations of the embodiments pertaining to the disclosure are specifically embraced by the present disclosure and are disclosed herein just as if each and every combination was individually and explicitly disclosed. In addition, all sub-combinations of the various embodiments and elements thereof are also specifically embraced by the present Attorney Docket: 048536-772001WO disclosure and are disclosed herein just as if each and every such sub combination was individually and explicitly disclosed herein. Compounds _{[0067] In one aspect, provided is a compound of Formula (I),} , or a pharmaceutically acceptable

¹⁸F; R² is H, D, ¹⁹F, or unsubstituted C1-C5 alkyl; R³ is H, D, ¹⁹F, or unsubstituted C1-C5 alkyl; and R^x is H, methyl, or ethyl. In embodiments, R² is H, D, ¹⁹F, or unsubstituted C₁-C₃ alkyl; and R³ is H, D, ¹⁹F, or unsubstituted C₁-C₃ alkyl. In embodiments, the alkyl is linear or branched, and is fully saturated. In embodiments, R² is H, D, ¹⁹F, or methyl; and R³ is H, D, ¹⁹F, or methyl. In embodiments, R^x is H, methyl, or ethyl. In embodiments, R^x is H or methyl. In embodiments, R^x is H. In embodiments, R^x is methyl. _{[0068] In embodiments, the compound of Formula (I) has the structure of Formula (Ia),} , or a pharmaceutically acceptable R² is H, D, ¹⁹F, or unsubstituted C1-C5 alkyl; R³ is H, D, ¹⁹F, or

R^x is H, methyl, or ethyl. In embodiments, the alkyl is linear or branched, and is fully saturated. In embodiments, R² is H, D, ¹⁹F, or unsubstituted C1-C3 alkyl; and R³ is H, D, ¹⁹F, or unsubstituted C1-C3 alkyl. In embodiments, R² is H, D, ¹⁹F, or methyl; and R³ is H, D, ¹⁹F, or methyl. In embodiments, R^x is H, methyl, or ethyl. In embodiments, R^x is H or methyl. In embodiments, R^x is H. In embodiments, R^x is methyl. Attorney Docket: 048536-772001WO _{[0069] In embodiments, the compound of Formula (I) or (Ia) is selected from the group} consisting of: , or a

ethyl. In embodiments, R^x is H or methyl. In embodiments, R^x is H. In embodiments, R^x is methyl. _{[0070] In embodiments, the compound is selected from the group consisting of:} , or a ethyl. In

or methyl. _{[0071] In embodiments, the compound is [18F]FMA, which has the structure:} , wherein R^x is H, or a _{[0072] In embodiments, the}

_{(S)-[18F]FMA and (R)-[18F]FMA:} Attorney Docket: 048536-772001WO

wherein the compound is a racemic mixture of (S)-[¹⁸F]FMA and (R)-[¹⁸F]FMA (i.e., a 1:1 ratio). In embodiments, the compound is a non-racemic mixture of (S)-[¹⁸F]FMA and (R)-[¹⁸F]FMA. _{[0073] In embodiments, the compound is (S)-[18F]FMA substantially free of (R)-[18F]FMA.} _{[0074] In embodiments, the compound is (R)-[18F]FMA substantially free of (S)-[18F]FMA.} _{[0075] The compounds of Formula (I) or (Ia) may be present as α or β anomers. In} embodiments, the compounds are in α form, e.g. α-(S)-[¹⁸F]FMA or α-(R)-[¹⁸F]FMA. In embodiments, the compounds are in β form, e.g. α-(S)-[¹⁸F]FMA or β-(R)-[¹⁸F]FMA. In embodiments, the compounds are a mixture of α and β forms. In embodiments, the compounds are a mixture of α and β forms, wherein the ratio of α to β is 1:1 or greater. In embodiments, the compounds are a mixture of α and β forms, wherein the ratio of α to β is 1.6:1 or greater. In embodiments, the compounds are a mixture of α and β forms, wherein the ratio of α to β is 2:1 or greater. In embodiments, the compounds are a mixture of α and β forms, wherein the ratio of α to β is 3:1 or greater. In embodiments, the compounds are a mixture of α and β forms, wherein the ratio of α to β is 4:1 or greater. In embodiments, the compounds are a mixture of α and β forms, wherein the ratio of α to β is 5:1 or greater. In embodiments, the compounds are in α form and are substantially free of β form. _{[0076] In another aspect, provided is a compound of Formula (II),} or a pharmaceutically acceptable R² is H, D, ¹⁹F, or unsubstituted C1-C5 alkyl; R³ is H, D, ¹⁹F, or

R^x is H, methyl, or ethyl. In embodiments, R² is H, D, ¹⁹F, or unsubstituted C1-C3 alkyl; and R³ is H, D, ¹⁹F, or unsubstituted Attorney Docket: 048536-772001WO C₁-C₃ alkyl. In embodiments, the alkyl is linear or branched, and is fully saturated. In embodiments, R² is H, D, ¹⁹F, or methyl; and R³ is H, D, ¹⁹F, or methyl. In embodiments, R^x is H, methyl, or ethyl. In embodiments, R^x is H or methyl. In embodiments, R^x is H. In embodiments, R^x is methyl. _{[0077] In embodiments, the compound of Formula (II) has the structure of Formula (IIa):} , or a pharmaceutically

R² is H, D, ¹⁹F, or unsubstituted C1-C5 alkyl; R³ is H, D, ¹⁹F, or unsubstituted C1-C5 alkyl; and R^x is H, methyl, or ethyl. In embodiments, R² is H, D, ¹⁹F, or unsubstituted C₁-C₃ alkyl; and R³ is H, D, ¹⁹F, or unsubstituted C1-C3 alkyl. In embodiments, the alkyl is linear or branched, and is fully saturated. In embodiments, R² is H, D, ¹⁹F, or methyl; and R³ is H, D, ¹⁹F, or methyl. In embodiments, R^x is H, methyl, or ethyl. In embodiments, R^x is H or methyl. In embodiments, R^x is H. In embodiments, R^x is methyl. _{[0078] In embodiments, the compound of Formula (II) or (IIa) is selected from the group} consisting of: , or a In

_{[0079] In another aspect, provided is a compound of Formula (III):} Attorney Docket: 048536-772001WO ,

or a pharmaceutically and R^x is H, methyl, or ethyl. In embodiments, R^x is H or methyl. In embodiments, R^x is H. In embodiments, R^x is methyl. _{[0080] In embodiments, the compound of Formula (III) has the structure of Formula (IIIa),} or a pharmaceutically

or ethyl. In embodiments, R^x is H or methyl. In embodiments, R^x is H. In embodiments, R^x is methyl. _{[0081] In embodiments, the compound of Formula (III) or (IIIa) is:} , or a _{[0082] In}

(_IV) , or a pharmaceutically and R^x is H, methyl, or ethyl.. In embodiments, R^x is H. In

Attorney Docket: 048536-772001WO Pharmaceutical compositions _{[0083] In another aspect, provided is a pharmaceutical composition including a compound as} disclosed herein, and a pharmaceutically acceptable excipient. _{[0084] In embodiments, provided is a pharmaceutical composition including a compound of} Formula (I), or a pharmaceutically acceptable salt thereof. In embodiments, provided is a pharmaceutical composition including a compound of Formula (I). _{[0085] In embodiments, provided is a pharmaceutical composition including a compound of} Formula (II), or a pharmaceutically acceptable salt thereof. In embodiments, provided is a pharmaceutical composition including a compound of Formula (II). Methods _{[0086] In another aspect, provided is a method of detecting bacteria in a subject, the method} including (_{i) administering an imaging agent including an 18F label to the subject;} _{(ii) allowing the bacteria in the subject to incorporate the 18F label intracellularly,} or into the bacterial cell wall of the bacteria, thereby forming ¹⁸F labeled bacteria; and (_{iii) detecting the 18F label, thereby detecting the bacteria in the subject.} In embodiments, the methods include allowing the bacteria in the subject to incorporate the ¹⁸F label intracellularly in the periplasmic space. _{[0087] In another aspect, provided is a method of detecting bacteria in a subject, the method} including (_{iv) administering an imaging agent including an 18F label to the subject;} _{(v) allowing the bacteria in the subject to incorporate the 18F label intracellularly,} or into the bacterial cell wall of the bacteria, thereby forming an ¹⁸F labeled bacteria; and (_{vi) detecting the 18F labeled bacteria in the subject.} In embodiments, the methods include allowing the bacteria in the subject to incorporate the ¹⁸F label intracellularly in the periplasmic space. _{[0088] In another aspect, provided is a method of detecting bacteria in a subject, the method} including (_{i) administering an imaging agent including an 18F label to the subject;} Attorney Docket: 048536-772001WO (_{ii) allowing the bacteria in the subject to incorporate the 18F label intracellularly,} into the bacterial cell wall, or into the periplasmic space of the bacteria, thereby forming ¹⁸F labeled bacteria; and (_{iii) detecting the 18F label, thereby detecting the bacteria in the subject.} _{[0089] In another aspect, provided is a method of detecting bacteria in a subject, the method} including (_{iv) administering an imaging agent including an 18F label to the subject;} _{(v) allowing the bacteria in the subject to incorporate the 18F label intracellularly,} into the bacterial cell wall, or into the periplasmic space of the bacteria, thereby forming an ¹⁸F labeled bacteria; and (_{vi) detecting the 18F labeled bacteria in the subject.} _{[0090] In embodiments of the methods disclosed herein, the imaging agent including an 18F} label is a compound of Formula (I) or (Ia), or a pharmaceutically acceptable salt thereof, as described herein. In embodiments, the imaging agent including an ¹⁸F label is a compound of Formula (I) or (Ia) and is selected from the group consisting of: , or a including an ¹⁸F label is a

of: Attorney Docket: 048536-772001WO ,

or a or In embodiments, R^x is H or methyl. In embodiments, R^x is H. In embodiments, R^x is methyl. _{[0091] In embodiments, the imaging agent including an 18F label is a compound of Formula} (II) or (IIa), or a pharmaceutically acceptable salt thereof, as described herein. In embodiments, the imaging agent including an ¹⁸F label is a compound of Formula (I) or (Ia) and is selected from the group consisting of: , or a

In embodiments, R^x is H or methyl. In embodiments, R^x is H. In embodiments, R^x is methyl. _{[0092] In embodiments of the methods disclosed herein, step (i) of administering an imaging} agent including an ¹⁸F label to the subject, includes administering an effective amount of the imaging agent including the ¹⁸F label to the subject. In embodiments, step (i) includes intravenous injection of the imaging agent including an ¹⁸F label. In embodiments, step (i) includes intravenous injection of an effective amount of the imaging agent including an ¹⁸F label. _{[0093] In embodiments of the methods disclosed herein, step (ii) of allowing the bacteria in} the subject to incorporate the ¹⁸F label intracellularly, or into the bacterial cell wall of the bacteria, thereby forming ¹⁸F labeled bacteria, includes waiting for a defined time period after step (i) and prior to step (iii). In embodiments of the methods disclosed herein, step (ii) of allowing the bacteria in the subject to incorporate the ¹⁸F label intracellularly, into the bacterial cell wall, or into the periplasmic space of the bacteria, thereby forming ¹⁸F labeled bacteria, includes waiting for a defined time period after step (i) and prior to step (iii). Attorney Docket: 048536-772001WO _{[0094] In embodiments, step (ii) of allowing the bacteria in the subject to incorporate the 18F} label intracellularly or into the bacterial cell wall of the bacteria, thereby forming an ¹⁸F labeled bacteria, includes incorporating the ¹⁸F label intracellularly into the cytoplasm. In embodiments, step (ii) of allowing the bacteria in the subject to incorporate the ¹⁸F label intracellularly or into the bacterial cell wall of the bacteria, thereby forming an ¹⁸F labeled bacteria, includes incorporating the ¹⁸F label intracellularly into the periplasmic space. In embodiments, step (ii) of allowing the bacteria in the subject to incorporate the ¹⁸F label intracellularly or into the bacterial cell wall of the bacteria, thereby forming an ¹⁸F labeled bacteria, includes incorporating the ¹⁸F label into the cell wall. _{[0095] In embodiments of the methods disclosed herein, step (iii) of detecting the 18F label,} thereby detecting the bacteria in the subject, includes performing a PET scan of the subject. In embodiments, step (iii) includes performing a dynamic PET scan of the subject. In embodiments of the methods disclosed herein, step (iii) of detecting the ¹⁸F labeled bacteria in the subject includes performing a PET scan of the subject. In embodiments, step (iii) includes performing a dynamic PET scan of the subject. _{[0096] In embodiments of the methods disclosed herein, the method further includes:} _{(v) administering the therapeutic agent to the subject;} _{(vi) allowing the bacteria in the subject to respond to the therapeutic agent; and} _{(vii) monitoring the therapeutic effect of the therapeutic agent.} _{[0097] In embodiments of the methods disclosed herein, the method further includes:} _{(iv) selecting a therapeutic agent for treating the bacteria in the subject;} _{(v) administering the therapeutic agent to the subject;} _{(vi) allowing the bacteria in the subject to respond to the therapeutic agent; and} _{(vii) monitoring the therapeutic effect of the therapeutic agent.} _{[0098] In embodiments, the therapeutic agent is an antibiotic. In some embodiments, the} therapeutic is a small molecule antibiotic. In some embodiments, the therapeutic is a peptide antibiotic. In some embodiments, the therapeutic is a glycopeptide antibiotic. In some embodiments, the therapeutic is a lipopeptide antibiotic. In some embodiments, the therapeutic is a macrocyclic antibiotic. In embodiments, step (vi) of allowing the bacteria in the subject to respond to the therapeutic agent includes waiting for a period of time before performing step Attorney Docket: 048536-772001WO (vii). In embodiments, the period of time is about 1 day, 2 days, 3, days, 4 days, 5 days, 6 days, 1 week, and/or 2 weeks. _{[0099] In embodiments, step (v) of administering the therapeutic agent to the subject includes} administering the therapeutic agent according to a dose regimen, e.g. a daily dose regimen. In embodiments, step (vii) of monitoring the therapeutic effect of the therapeutic agent is performed after the first administration of the therapeutic agent. In embodiments, step (vii) is performed about 1 day, 2 days, 3, days, 4 days, 5 days, 6 days, 1 week, and/or 2 weeks after the first administration of the therapeutic agent. _{[0100] In embodiments, step (vii) of monitoring the therapeutic effect of the therapeutic agent} includes: (vii-1) administering an effective amount of the imaging agent including an ¹⁸F label to the subject; (vii-2) allowing the bacteria in the subject to incorporate the ¹⁸F label intracellularly, into the bacterial cell wall, or into the periplasmic space of the bacteria, thereby forming ¹⁸F labeled bacteria; and (vii-3) detecting the ¹⁸F label, thereby detecting the bacteria in the subject. _{[0101] In embodiments, step (vii) of monitoring the therapeutic effect of the therapeutic agent} includes: (vii-1) administering an effective amount of the imaging agent including an ¹⁸F label to the subject; (vii-2) allowing the bacteria in the subject to incorporate the ¹⁸F label intracellularly, into the bacterial cell wall, or into the periplasmic space of the bacteria, thereby forming an ¹⁸F labeled bacteria; and (vii-3) detecting the ¹⁸F labeled bacteria in the subject. _{[0102] In embodiments, step (vii-3) of detecting the 18F label or 18F labeled bacteria in the} _{subject includes detecting a change in the amount of the 18F label or 18F labeled bacteria, relative} to the detection from step (iii). In embodiments, step (vii-3) includes detecting a change in the degree of incorporation of the ¹⁸F label into the bacteria, relative to the detection from step (iii). In embodiments, step (vii-3) includes detecting a change in the intensity of the PET signal in the subject, relative to the detection from step (iii). In embodiments, step (vii-3) includes detecting a decrease in the intensity of the PET signal in the subject, relative to the detection from step Attorney Docket: 048536-772001WO (iii). In embodiments, step (vii-3) includes detecting an increase in the intensity of the PET signal in the subject, relative to the detection from step (iii). In embodiments, step (vii-3) includes detecting a change in the localization of the ¹⁸F label in the subject, relative to the detection from step (iii). In embodiments, step (vii-3) includes detecting a change in the tissues in which the ¹⁸F label is detected in the subject, relative to the detection from step (iii). In embodiments, step (vii-3) includes detecting a reduction in size of the regions in which the ¹⁸F label is detected in the subject, relative to the detection from step (iii). _{[0103] In embodiments, step (vii) of monitoring the therapeutic effect of the therapeutic agent} includes: (vii-1) administering an effective amount of the imaging agent including an ¹⁸F label to the subject; (vii-2) allowing the bacteria in the subject to incorporate the ¹⁸F label intracellularly, into the bacterial cell wall, or into the periplasmic space of the bacteria, thereby forming ¹⁸F labeled bacteria; (vii-3) detecting the ¹⁸F label, thereby detecting the bacteria in the subject; and (vii-4) identifying a change from the detection from step (iii) to the detection from step (vii-3). _{[0104] In embodiments, step (vii) of monitoring the therapeutic effect of the therapeutic agent} includes: (vii-1) administering an effective amount of the imaging agent including an ¹⁸F label to the subject; (vii-2) allowing the bacteria in the subject to incorporate the ¹⁸F label intracellularly, into the bacterial cell wall, or into the periplasmic space of the bacteria, thereby forming an ¹⁸F labeled bacteria; (vii-3) detecting the ¹⁸F labeled bacteria in the subject; and (vii-4) identifying a change from the detection from step (iii) to the detection from step (vii-3). _{[0105] In embodiments, step (vii-1) of administering an imaging agent including an 18F label} to the subject, includes administering an effective amount of the imaging agent including the ¹⁸F label to the subject. In embodiments, step (vii-1) includes intravenous injection of the imaging Attorney Docket: 048536-772001WO agent including an ¹⁸F label. In embodiments, step (vii-1) includes intravenous injection of an effective amount of the imaging agent including an ¹⁸F label. _{[0106] In embodiments of the methods disclosed herein, step (vii-2) of allowing the bacteria} in the subject to incorporate the ¹⁸F label intracellularly, into the bacterial cell wall, or into the periplasmic space of the bacteria, thereby forming ¹⁸F labeled bacteria, includes waiting for a defined time period after step (vii-1) and prior to step (vii-3). _{[0107] In embodiments of the methods disclosed herein, step (vii-3) of detecting the 18F label,} thereby detecting the bacteria in the subject, includes performing a PET scan of the subject. In embodiments, step (vii-3) includes performing a dynamic PET scan of the subject. In embodiments of the methods disclosed herein, step (vii-3) of detecting the ¹⁸F labeled bacteria in the subject includes performing a PET scan of the subject. In embodiments, step (vii-3) includes performing a dynamic PET scan of the subject. _{[0108] In embodiments, step (vii-4) of identifying a change from the detection from step (iii)} to the detection from step (vii-3), includes detecting a change in the localization of the ¹⁸F label in the subject. In embodiments, step (vii-4) of identifying a change from the detection from step (iii) to the detection from step (vii-3), includes detecting a change in the tissues in which the ¹⁸F label is detected in the subject. In embodiments, step (vii-4) of identifying a change from the detection from step (iii) to the detection from step (vii-3), includes detecting a reduction in size of the regions in which the ¹⁸F label is detected in the subject. _{[0109] In embodiments, step (vii-4) of identifying a change from the detection from step (iii)} to the detection from step (vii-3), includes detecting a change in the intensity of the PET signal in the subject. In embodiments, step (vii-4) of identifying a change from the detection from step (iii) to the detection from step (vii-3), includes detecting a decrease in the intensity of the PET signal in the subject. In embodiments, step (vii-4) of identifying a change from the detection from step (iii) to the detection from step (vii-3), includes detecting an increase in the intensity of the PET signal in the subject. _{[0110] In embodiments of the methods disclosed herein, the method is a method of detecting} one or more bacteria selected from the group consisting of S. aureus, methicillin-resistant S. aureus (MRSA), Staphylococcus epidermidis, Enterococcus faecalis, Listeria monocytogenes, E. coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Proteus mirabilis, Acinetobacter baumannii, Salmonella typhimurium, and Enterobacter cloacae. In embodiments, the method is Attorney Docket: 048536-772001WO a method of detecting one or more bacteria selected from the group consisting of S. aureus, methicillin-resistant S. aureus (MRSA), Staphylococcus epidermidis, Enterococcus faecalis, E. coli, and Proteus mirabilis. _{[0111] In embodiments, the method is a method of detecting gram-positive bacteria. In} embodiments, the method is a method of detecting a gram-positive bacteria selected from the group consisting of S. aureus, methicillin-resistant S. aureus (MRSA), Staphylococcus epidermidis, Enterococcus faecalis, and Listeria monocytogenes. In embodiments, the method is a method of detecting gram-positive bacteria. In embodiments, the method is a method of detecting a gram-positive bacteria selected from the group consisting of S. aureus, methicillin- resistant S. aureus (MRSA), Staphylococcus epidermidis, and Enterococcus faecalis. In embodiments, the method is a method of detecting a gram-positive bacteria selected from the group consisting of S. aureus and methicillin-resistant S. aureus (MRSA). In embodiments, the method is a method of detecting gram-positive bacteria wherein the imaging agent including an ¹⁸F label is rac-[¹⁸F]FMA. In embodiments, the method is a method of detecting gram-positive bacteria wherein the imaging agent including an ¹⁸F label is (S)-[¹⁸F]FMA. In embodiments, the method is a method of detecting gram-positive bacteria wherein the imaging agent including an ¹⁸F label is I-[¹⁸F]FMA. _{[0112] In embodiments, the method is a method of detecting gram-negative bacteria. In} embodiments, the method is a method of detecting gram-negative bacteria selected from the group consisting of E. coli, P. aeruginosa, K. pneumoniae, P. mirabilis, Acinetobacter baumannii, Salmonella typhimurium, and Enterobacter cloacae. In embodiments, the method is a method of detecting gram-negative bacteria selected from the group consisting of E. coli, K. pneumoniae, and P. mirabilis. In embodiments, the method is a method of detecting gram- negative bacteria wherein the imaging agent including an ¹⁸F label is (S)-[¹⁸F]FMA. Kits _{[0113] Also provided herein are kits including the compounds described herein, or} pharmaceutical compositions provided and described herein, as well as written instructions for making and using the same. In embodiments, the kits of the disclosure further include one or more syringes (including pre-filled syringes) used to administer one any of the provided compounds or pharmaceutical compositions to a subject. Attorney Docket: 048536-772001WO _{[0114] Any of the above-described and kits can further include one or more additional} reagents, where such additional reagents can be selected from: dilution buffers; reconstitution solutions, and the like. _{[0115] In embodiments, the components of a kit can be in separate containers. In some other} embodiments, the components of a kit can be combined in a single container. _{[0116] In embodiments, a kit can further include instructions for using the components of the} kit to practice the methods. The instructions for practicing the methods are generally recorded on a suitable recording medium. For example, the instructions can be printed on a substrate, such as paper or plastic, etc. The instructions can be present in the kits as a package insert, or in the labeling of the container of the kit or components thereof (i.e., associated with the packaging or sub-packaging), etc. The instructions can be present as an electronic storage data file present on a suitable computer readable storage medium, e.g. CD-ROM, diskette, flash drive, etc. In some instances, the actual instructions are not present in the kit, but means for obtaining the instructions from a remote source (e.g., via the internet), can be provided. An example of this embodiment is a kit that includes a web address where the instructions can be viewed and/or from which the instructions can be downloaded. As with the instructions, this means for obtaining the instructions can be recorded on a suitable substrate. _{[0117] Throughout this specification, various patents, patent applications and other types of} publications (e.g., journal articles, electronic database entries, etc.) are referenced. The disclosure of all patents, patent applications, and other publications cited herein are hereby incorporated by reference in their entirety for all purpose. _{[0118] No admission is made that any reference cited herein constitutes prior art. The} discussion of the references states what their authors assert, and the inventors reserve the right to challenge the accuracy and pertinence of the cited documents. It will be clearly understood that, although a number of information sources, including scientific journal articles, patent documents, and textbooks, are referred to herein; this reference does not constitute an admission that any of these documents forms part of the common general knowledge in the art. _{[0119] The discussion of the general methods given herein is intended for illustrative} purposes only. Other alternative methods and alternatives will be apparent to those of skill in the art upon review of this disclosure, and are to be included within the spirit and purview of this application. Attorney Docket: 048536-772001WO EXAMPLES _{[0120] Additional embodiments are disclosed in further detail in the following examples,} which are provided by way of illustration and are not in any way intended to limit the scope of this disclosure or the claims. _{[0121] General. All chemical reagents were purchased from Sigma-Aldrich and Chem Scene} and used without further purification. Reactions were monitored using pre-coated silica gel plates (Merck, silica gel 60 F254). Flash column chromatography was performed on silica gel (Merck, 230-400 mesh).¹H and ¹³C NMR spectra were obtained on a Bruker Avance III HD 400 MHz NMR instrument. High-resolution mass spectroscopy (HRMS) services were also performed. All bacterial strains were purchased from American Type Culture Collection (ATCC) except S. aureus Xen29, E. coli Xen14 and P. aeruginosa Xen41 which were purchased from PerkinElmer, and a Methicillin-Resistant S. aureus clinical isolate which was provided by the University of Nebraska Medical Center. [¹⁸F]fluoride ion was generated by the nuclear reaction of ¹⁸O(p,n)¹⁸F in a target of enriched [¹⁸O]H₂O using a PET trace 18 MeV cyclotron (GE Healthcare, Buckinghamshire U.K.). Radio TLC analysis was performed on a radio TLC scanner (Bioscan AR200, Bioscan Inc.). PET/CT imaging of mice was performed by a Siemens Inveon micro-PET/CT (Siemens, Erlangen, Germany). The radioactivity for in vitro and ex vivo analysis was measured on a Hidex Automatic Gamma Counter (Turku, Finland). E^XAMPLE 1 Synthesis of (S)- and (R)-[¹⁸F]FMA OH r ¹⁸ OH B F O OH O OH 1⁸F ,

, , (0.25 mg, 1.0 umol), 0.1% TEA/DMSO (100 uL), 60 ^oC, 10 min. _{[0123] Radiochemistry. [18F]fluoride ion (3mL in enriched [18O]H2O) was passed through the} female side of a Chromafix-HCO3 cartridge (ABX advanced biochemical compounds GmbH, Radeberg, Germany) preconditioned with 2 mL of EtOH and 8 mL of water. The retained Attorney Docket: 048536-772001WO [¹⁸F]fluoride ion was eluted into a reaction vial (4 mL) from the male side of the cartridge using a solution of Cs2CO3 (2.2 mg, 6.8 umol) in 90% MeOH/Water (1 mL). The solvent was removed un- der an N2 stream with reduced pressure at 90 ^oC. Azeotropic distillation of the mixture with ¹⁸F ion was performed using acetonitrile (1.0 mL x 2) under the same conditions. _{[0124] Step (a). 4-Nitrophenyl-2-bromopropanoate (8 mg, 29.2 umol) dissolved in 80%} tBuOH/MeCN (0.5 mL) was added to the reaction vial, then stirred at 110 ^oC for 10 min. After the reaction, the crude mixture was cooled in an ice bath and diluted with 20 mL of water. The mixed solution was passed through a tC18 Sep-Pak cartridge, then eluted with MeCN (1.5 mL). The crude mixture eluted from the cartridge was diluted with water (1.5 mL) and injected into an HPLC system (Phenomenex, Luna 10 μm C18 column, 250 × 10 mm; 45% MeCN/Water containing 0.1% trifluoroacetic acid; A = 254 nm, flow rate = 4.0 mLmin⁻¹) to collect the [¹⁸F]NFP (T_R = 19 min). [¹⁸F]NFP in HPLC eluent (typically 4-5 mL) was diluted with 18 mL of water, then loaded into the tC18 Sep-Pak cartridge. Then, the female side of the Sep-Pak dry sodium sulfate Plus Long Cartridge (without preconditioning) was connected to the male side of a tC18 Sep-Pak Cartridge containing [¹⁸F]NFP. An additional 2 mL of Et2O was passed through the female side of the cartridges connected in series. The collected solution of [¹⁸F]NFP in a 4 mL vial was dried under an N₂ stream under reduced pressure at room temperature. _{[0125] [18F]NFP was obtained from 4-nitro-phenyl-2-bromopropanoate in 12.8 ± 3.4%} radiochemical yield (n = 12, non-decay corrected) with high radiochemical purity (>99%), and molar activity (78.6 ± 32.2 GBq/umol) after HPLC purification. The radiochemical identity of [¹⁸F]NFP was confirmed by co-injection with ¹⁹F standard using analytical HPLC. _{[0126] Step (b). After complete drying of [18F]NFP, the muramic acid (0.25 mg, 1.0 umol)} dissolved in 100 uL of DMSO containing 0.1 % TEA (v/v) was added to the reaction vial and heated at 60 °C for 10 min. The mixture was diluted by 5% EtOH/Water containing 0.1 % HCl (0.9 mL), then injected into the HPLC system (Phenomenex, Luna 10 μm C18 column, 250 × 10 mm; 5% EtOH/Water containing 0.1% HCl; A = 210 nm, flow rate = 4.0 mLmin−¹). Since racemic [¹⁸F]NFP was used for the coupling reaction, four diastereomers were observed on HPLC chromatogram (TR = 6.1, 7.1, 16.3, and 19.9 min) with hydrolyzed [¹⁸F]NFP (<5%, 2- [¹⁸F]fluoropropanoic acid, TR = 8.2 min; confirmed by co-injection) and an unknown peak (<5%, T_R= 5.5 min) (see FIG.3). Among the products, two major diastereomers α-(S)-[¹⁸F]FMA (T_R = 16.3 min) and α-(R)-[¹⁸F]FMA) (T_R = 19.9 min) were isolated after the reaction. Attorney Docket: 048536-772001WO _{[0127] Both (R)- and (S)-[18F]FMA in HPLC eluent (typically 4-5 mL) were diluted with 18 mL} of acetonitrile, then loaded onto a Plus NH2 Sep-Pak cartridge. Finally (R)- and (S)-[¹⁸F]FMA were eluted using a saline (1.5 mL), ready for in vitro or in vivo studies. The radiochemical purities of both (R)- and (S)-[¹⁸F]FMA were confirmed by analytical HPLC (Phenomenex, Luna 10 μm C18 column, 250 × 4.6 mm; 5% EtOH/Water containing 0.1% HCl; A = 210 nm, flow rate = 1.0 . _{[0128] α-(S)-[18F]FMA and α-(R)-[18F]FMA were collected respectively from the HPLC system} with 35.0 ± 3.6% radiochemical yield (non-decay corrected, calculated from the isolated activity of [¹⁸F]NFP), high radiochemical purity (>99%), and molar activity (57.4 ± 23.5 GBq/umol) after formulation in saline using Plus NH₂ Sep-Pak. The total synthesis time was 90 min. _{[0129] Using an amine-reactive 18F-prosthetic agent yielded a time- and cost-effective} radiosynthesis of ¹⁸F labeled N-acetyl muramic acid. EXAMPLE 2 In vitro stability of (S)- and (R)-[¹⁸F]FMA α-β interconversion _{[0130] The equilibration of α-β sugars is a well-known process in aqueous solution at ambient} conditions, which may be accelerated at high temperatures (>80 ^oC). Time-dependent α-β interconversion of (S)-[¹⁸F]FMA and (R)- [¹⁸F]FMA after HPLC purification (0, 30, 60, 120, and 240 min) at ambient conditions was monitored by analytical HPLC (Phenomenex; Luna 10 μm C18250x4.6 mm; 5% EtOH/Water containing 0.1% HCl; 1 mLmin^-1) (see FIG.4, FIG.5). _{[0131] Isolated α-(S)- and α-(R)-[18F]FMA showed α-β interconversion at ambient conditions.} The α- β interconversions of α-(S)- and α-(R)-[¹⁸F]FMA were equilibrated to approximately 1.6(α):1(β) ratio after 4 h (see FIG.4, FIG.5), confirmed by analytical HPLC with corresponding ¹⁹F standards before and after equilibrium. _{[0132] To assess mutarotation of the α-β anomers at elevated temperature, isolated α-(S)- and} α-(R)- [¹⁸F]FMA were heated at 90 ^oC for 10 min to speed up the α-β interconversion, then analyzed by analytical-HPLC. After heating, the β anomers were generated from the corre- sponding α-(S)- and α-(R)- [¹⁸F]FMA. β-(S)- and β-(R)- [¹⁸F]FMA were isolated from the mixture using a semi-prep HPLC system and confirmed by analytical-HPLC. Again, isolated β- Attorney Docket: 048536-772001WO (S)- and β-(R)-[¹⁸F]FMA were heated at 90 ^oC for 10 min, and finally, it was confirmed that α- (S)- and α-(R)-[¹⁸F]FMA were generated from corresponding β-(S)- and β-(R)-[¹⁸F]FMA. _{[0133] Due to the short fluorine-18 half-life (109.8 min), all in vitro and in vivo studies were} conducted immediately after HPLC purification of corresponding α-anomers instead of preparing α,β equilibrated (S)-and (R)-[¹⁸F]FMA. Stability in serum _{[0134] Saline, mouse serum, or human serum (0.5 mL) was incubated with (S)- and (R)-} [¹⁸F]FMA (3.7 MBq), respectively, at 37 °C for 0, 15, 30, 60, and 90 min (n = 3 for each time point). Each sample was diluted with acetonitrile (0.5 mL), then centrifuged at 3500 rpm for 5 min. The collected supernatants were analyzed using radio-thin layer chromatography (radio- TLC) by developing at 65% MeCN/Water. Both (S)- and (R)-[¹⁸F]FMA were intact in saline, mouse serum, and human serum for 90 min. EXAMPLE 3 In vitro uptake of (S)- and (R)-[¹⁸F]FMA _{[0135] Each bacterial strain was aerobically grown overnight in a shaking incubator at 37 oC in} media. Overnight cultures were diluted to an optical density at 600 nm (OD600) of 0.05 and grown to exponential phase (~ 0.4). In vitro uptake assays were conducted by incubating bacteria cultures with 30 uL from the stock solution of (S)- and (R)-[¹⁸F]FMA (29.6 MBq/mL) at 37 ^oC for 90 min. As controls, heat-killed (H.K.) bacteria (pre-treated at 90 ^oC for 30 min) were incubated in the same conditions with radiotracers. The bacterial cultures were incubated with unlabeled muramic acid (0.1 mM) and radiotracers in the same conditions for the blocking experiments. Aliquots of bacterial cultures (300 uL) were centrifuged at 13200 rpm for 6 min and washed with PBS (300 uL). The radioactivity of the pellets and supernatants were measured using a gamma counter (Hidex, Turku, Finland). The in vitro data were normalized to CFUs to account for differential growth rates between organisms. The non-specific binding of both tracers in the filter membrane were measured by incubating (S)- and (R)-[¹⁸F]FMA in the media without bacteria at 37 ^oC for 90 min. _{[0136] Both (S)- and (R)-[18F]FMA showed robust accumulation by several human pathogens} in vitro including methicillin-resistant S. aureus. An in vitro uptake assay of (S)- and (R)- Attorney Docket: 048536-772001WO [¹⁸F]FMA in S. aureus and Escherichia coli, key gram-positive and negative bacterial pathogens, was initially performed to evaluate the sensitivity and specificity of (S)- and (R)- [¹⁸F]FMA. A slightly higher uptake of (R)-[¹⁸F]FMA was observed in S. aureus versus that of (S)-[¹⁸F]FMA (1.4-fold, P < 0.0001). On the other hand, (S)-[¹⁸F]FMA showed significantly higher uptake (23.1-fold, P < 0.0001) in E. coli than that of (R)-[¹⁸F]FMA. The specificity of both (S)- and (R)-[¹⁸F]FMA was demonstrated by incubating them with heat-killed or unlabeled ‘blocking” N-acetyl muramic acid (0.1 mM) in S. aureus and E. coli, respectively (FIG.6, FIG. 7). Based on the α-β interconversion of [¹⁸F]FMA, an in vitro assay in S. aureus was conducted after α-β equilibration (4h following formulation) to investigate the uptake efficiency of α versus β anomers. After α-β equilibration, slightly reduced uptake of (S)- (0.8-fold, P < 0.0080) and (R)-[¹⁸F]FMA (0.8-fold, P < 0.0012) in S. aureus were observed. These results suggest that the incorporation of the α anomer was slightly better than that of the β anomer. _{[0137] Next, the following gram-positive and gram-negative pathogens were screened to} explore the sensitivity of (S)- and (R)-[¹⁸F]FMA: S. aureus, S. aureus Xen29, methicillin- resistant S. aureus (MRSA), Staphylococcus epidermidis, Enterococcus faecalis, Listeria monocytogenes, E. coli, E. coli Xen14, Pseudomonas aeruginosa, P. aeruginosa Xen41, Klebsiella pneumoniae, Proteus mirabilis, Acinetobacter baumannii, Salmonella typhimurium, and Enterobacter cloacae. (R)-[¹⁸F]FMA showed high uptake in gram-positive bacteria pathogens except L. monocytogenes with lower uptake in gram-negative pathogens. On the other hand, (S)-[¹⁸F]FMA showed higher sensitivity to gram-negative pathogens (E. coli, E. coli Xen14, P. aeruginosa Xen41, K. pneumoniae, and P. mirabilis) than (R)-[¹⁸F]FMA. Interestingly, (S)-[¹⁸F]FMA showed significantly lower sensitivity in S. epidermidis compared with that of (R)-[¹⁸F]FMA. Incorporation in L. monocytogenes, P. aeruginosa, A. baumannii, S. typhimurium, and E. cloacae was low for both (S)- and (R)-[¹⁸F]FMA. See FIG.8. E^XAMPLE 4 In vivo PET imaging studies of (S)- and (R)-[¹⁸F]FMA _{[0138] Animals for PET imaging studies. All animal studies were approved by an} Institutional Animal Care and Use Committee and performed in accordance with guidelines. CBA/J mice (female, 9-11 weeks old, 20-24 g) were used for all experiments. All the animals were anesthetized with 5% isoflurane during infection and iPET/CT imaging. The murine Attorney Docket: 048536-772001WO myositis model used was generated (Parker, M. F et al., ACS Cent. Sci.2020, 6, 155–165) by inoculating with 50 uL of S. aureus, E. coli, or S. epidermidis (~10⁶ CFU) in the left shoulder muscle and 10X heat-killed (pre-treated at 90 °C for 30 min) bacteria in the right shoulder muscle. The infections were allowed to develop for 10 h prior to PET imaging. Upon iPET/CT imaging completion, mice were sacrificed immediately for biodistribution analysis. The radioactivity accumulated in harvested tissues was measured using a Hidex Automatic Gamma Counter (Hidex, Turku, Finland). _{[0139] μPET/CT imaging studies. The iPET/CT imaging studies were conducted using a} Siemens Inveon micro-PET-CT scanner (Siemens, Erlangen, Germany). For all studies, whole- body dynamic PET images of healthy or infected mice (n = 4 for each) were obtained with 53 frames (2s x 15, 5s x 6, 10s x 6, 30 s x 4, 60s x 6, 300s x 16 frames, respectively) for 90 min immediately after injection of (S)- and (R)-[¹⁸F]FMA (7.4 ± 1.8 MBq, 100 uL) via tail vein using a catheter, followed by a micro-CT scan for 10 min. All data were reconstructed into three- dimensional images to generate dynamic PET images and co-registered with CT images using open-source Amide software. _{[0140] Image analysis. Amide software was used for analyzing image data (Loening, A. M. et} al., Mol. Imaging 2003, 2, 131–137). The volumes of interest (VOI’s) were drawn manually for each organ (brain, liver, left ventricular chamber, lung, kidneys, and bladder) to obtain a PET- derived biodistribution profile in healthy mice. Identical volumes and shapes (spherical, 5-8 mm³) of VOI’s were drawn around the peak uptake of tracers for the right and left shoulder of the bacteria-infected mice (FIG.9). _{[0141] Radioactivity in the VOI’s at each time point was expressed as the standardized uptake} value (SUV), which is normalized to the injected radioactivity and body weight of mice and used to generate the time-activity curves (TAC) (FIG.10). The image-based blood TACs were generated based on the blood pool derived from LV chamber analysis. The kinetic parameters of radiotracers in each organ of healthy mice were calculated from TAC by fitting a biexponential curve using GraphPad Prism v9.0 software (GraphPad Software Inc., San Diego, California, USA) as following: distribution half-life (T1/2α), elimination half-life (T1/2β), peak concentration (Cmax), time at Cmax (Tmax), and area under the curve (AUC) (Table 1). Attorney Docket: 048536-772001WO [_{0142] Statistical analysis. All data were expressed as mean ± standard deviations. Statistical} analyses were conducted by an unpaired two-tailed Student’s t-test using GraphPad Prism v 9.0. P < 0.05 was considered statistically significant. Table 1: Kinetic parameters of (S)-[¹⁸F]FMA in normal mice. SUV: Standardized uptake value, T1/2: half-life (min), Cmax: peak concentration (SUV), Tmax: time at Cmax (min), AUC: area under the curve (SUV^min), n.d.: not determined.

- observed in healthy mice. Preliminary in vivo evaluation of (S)- and (R)-[¹⁸F]FMA was performed in healthy mice (CBA/J mice, 9-11 weeks old) to investigate any differences in distribution and stability depending on the stereochemistry of fluorine-18. Following intravenous injection, (S)-[¹⁸F]FMA showed early peak uptake in the blood, lung, liver, and brain (Tmax < 1 min), followed by rapid washout as shown in time activity curves (TACs) (FIG.9, FIG.10). The highest concentration of (S)-[¹⁸F]FMA was observed early in blood (Cmax = 6.5 ± 0.2 SUV), lung (Cmax = 3.0 ± 0.2 SUV), liver (Cmax = 1.9 ± 0.2 SUV), and brain

0.5 ± 0.0 SUV), followed by rapid clearance (T_1/2α = 1.1 ±0.4 min and T_1/2β = 13.0 ± 5.5 min in blood, T_1/2α = 1.2 ± 0.1 min and T_1/2β = 15.8 ± 1.2 min in lung, T_1/2α = 1.1 ± 0.2 min and T_1/2β = 18.4 ± 8.8 min in liver, and T1/2α = 1.3 ± 0.2 min and T1/2β = 18.5 ± 4.3 min in brain, respectively) (Table 1). These results suggested that both (S)- and (R)-[¹⁸F]FMA are immediately distributed to the whole-body via systemic and pulmonary circulation after intravenous injection. [_{0144] After rapid washout from those organs, (S)-[18F]FMA showed high kidney and bladder} uptake. The value of Cmax and AUC of (S)-[¹⁸F]FMA in the kidneys were 15- and 49-fold higher than that of the liver, suggesting that (S)-[¹⁸F]FMA has a dominant urinary excretion pathway rather than biliary excretion (Table 1). (R)-[¹⁸F]FMA showed similar distribution/excretion patterns to that of (S)-[¹⁸F]FMA (data not shown). The distribution and elimination half-lives were not significantly different

- and (R)-[¹⁸F]FMA in the blood, lung, liver, and brain. Both tracers showed high renal accumulation and retention over time, suggesting that the kidneys and bladder are the dose-limiting organs. Attorney Docket: 048536-772001WO _{[0145] Ex vivo biodistribution analysis was conducted immediately after iPET/CT imaging} studies. Both tracers showed similar distribution patterns in the organs and tissues, with less than 3 %IDg^-1 of radiotracer in all tissues except for the kidneys. Low bone uptake (<0.4 %IDg^-1) suggested high in vivo stability of both (S)-and (R)-[¹⁸F]FMA against ¹⁸F-defluorination (data not shown). _{[0146] Both (S)- and (R)-[18F]FMA could detect bacterial infection in a murine myositis} model. Based on in vitro results, three different bacterial pathogens (S. aureus, E. coli, and S. epidermidis) were used to generate a murine myositis model widely used to screen potential bacteria-specific radiotracers. Mice were inoculated with live bacteria in the left shoulder and a 10-fold higher concentration that of heat-killed in the right shoulder, respectively. At 10 hours post-injection, dynamic PET scanning was performed immediately 90 min post intravenous injection of (S)- and (R)-[¹⁸F]FMA, followed by a 10 min CT scan and ex vivo biodistribution analysis (FIG.11). _{[0147] (S)-[18F]FMA. μPET/CT images of (S)-[18F]FMA in both S. aureus and E. coli infected} mice showed significant tracer uptake at the site of live bacterial inoculation compared with that of heat-killed bacterial inoculation. Even though the accumulation of (S)-[¹⁸F]FMA at the site of live S. epidermidis injection was significantly lower than that of both S. aureus and E. coli, it was visually distinguishable from the heat-killed site, despite the relatively high background of (S)- [¹⁸F]FMA in this model (FIG.12, FIG.13). As shown in the TAC (FIG.14), (S)-[¹⁸F]FMA was rapidly accumulated in infected and inflamed muscle at early time points, with rapid tracer clearance from inflamed muscle and retention in infected muscle over time. The calculated AUC value from the TAC was higher in infected muscles (146.5 ± 16.4, 157.2 ± 29.3, and 57.5 ± 12.3 for S. aureus, E. coli, and S. epidermidis, respectively) than those of inflamed muscles (50.4 ± 1.5, 56.8 ± 14.8, and 37.6 ± 12.4 for S. aureus, E. coli, and S. epidermidis, respectively). The AUC ratio between infected- and inflamed muscle was 2.91 ± 0.37 (P <0.0001; S. aureus-infected), 2.85 ± 0.61 (P = 0.0061; E. coli-infected), 1.57 ± 0.18 (P = 0.1205; S. epidermidis-infected), and 1.04 ± 0.17 (P = 0.8147; healthy control). SUV ratios between infected and inflamed sites at 90 min post-injection of (S)-[¹⁸F]FMA were significantly higher (7.47 ± 0.87; P < 0.0001, 3.55 ± 0.84; P = 0.0024, and 1.65 ± 0.02; P = 0.0039 in S. aureus, E. coli, and S. epidermidis, respectively) than that of healthy mice (1.02 ± 0.21; P = 0.9109). These data were also supported by %IDg^-1 ratios (1.00 ± 0.17; n.s. in healthy control, 5.84 ± 1.48; P = 0.0075 in S. aureus, 2.89 ± 0.37; P Attorney Docket: 048536-772001WO < 0.0001 in E. coli, 2.04 ± 0.35; P = 0.0004 in S. epidermidis) which were obtained from ex vivo tissue analysis (FIG.13, FIG.14). _{[0148] (R)-[18F]FMA. (R)-[18F]FMA was also robustly accumulated at the site of live S. aureus} injection but not in that of heat-killed bacterial injection (FIG.15, FIG.16). (R)-[¹⁸F]FMA showed slightly higher in vitro uptake in S. aureus than (S)-[¹⁸F]FMA, but there was no significant difference in accumulation in vivo and ex vivo (In vivo: 1.72 ± 0.11 SUV for (S)-[¹⁸F]FMA, 1.98 ± 0.28 SUV for (R)-[¹⁸F]FMA; P = 0.1380. Ex vivo: 2.11 ± 0.44 %IDg^-1 for (S)-[¹⁸F]FMA, 2.55 ± 0.14 %IDg^-1 for (R)-[¹⁸F]FMA; P = 0.4408). _{[0149] Unlike (S)-[18F]FMA, (R)-[18F]FMA showed high accumulation at the site of live S.} epidermidis inoculation (SUV: 0.71 ± 0.00 vs.1.80 ± 0.25 for (S)- and (R)-[¹⁸F]FMA, respectively; P = 0.0014), but low in that of E. coli (SUV: 1.67 ± 0.20 vs.0.58 ± 0.23 for (S)- and (R)- [¹⁸F]FMA, respectively; P = 0.0037). _{[0150] The accumulated ratios (infected versus inflamed sites) of (R)-[18F]FMA were well} matched between PET-derived data (1.06 ± 0.18; n.s. in healthy control, 7.60 ± 0.14; P = 0.005 in S. aureus, 1.94 ± 0.38; P = 0.0603 in E. coli, 3.52 ± 1.38; P = 0.0020 in S. epidermidis) and ex vivo analysis (1.00 ± 0.12; P = 0.9712 in healthy control, 6.67 ± 2.73; P = 0.0043 in S. aureus, 2.02 ± 0.63; P = 0.0332 in E. coli, 3.82 ± 0.49; P = 0.0121 in S. epidermidis). _{[0151] (R)-[18F]FMA showed a similar accumulation/washout pattern between infected and} inflamed muscle versus that of (S)-[¹⁸F]FMA. The AUC ratio of (R)-[¹⁸F]FMA between infected- and inflamed muscle was 3.11 ± 0.77 (P = 0.0003; S. aureus-infected), 1.64 ± 0.24 (P = 0.2222; E. coli-infected), 2.31 ± 0.76 (P = 0.0387; S. epidermidis-infected), and 0.93 ± 0.07 (P = 0.3780; healthy control) (FIG.15, FIG.16, FIG.17). _{[0152] Tracer performance in vivo did not always correlate with in vitro results. For example,} (S)-[¹⁸F]FMA and (R)-[¹⁸F]FMA showed low uptake in vitro in S. epidermidis and E. coli, but were able to detect these organisms in vivo. The amount of non-specific binding of both tracers in the filter membrane (as a control; 0.05 ± 0.02 % of both tracers were retained) were measured to clarify the specificity of in vitro uptake values (data not shown). There were significant differences between the control and S. epidermidis (P < 0.0001), and (R)-[¹⁸F]FMA in E. coli (P < 0.0001), respectively. These results indicated low but existent uptake of (S)-[¹⁸F]FMA by S. epidermidis and (R)-[¹⁸F]FMA by E. coli explaining why these tracer/pathogen combinations demonstrated signals in vivo. Attorney Docket: 048536-772001WO _{[0153] Limit of detection. To investigate the limit of detection with variable CFUs of S.} aureus, mice were inoculated with 10⁴ and 10⁵ CFUs of live S. aureus in the left shoulder and a 10-fold higher concentration of heat-killed bacteria in the right shoulder, and studied using (R)- [¹⁸F]FMA. iPET/CT images of (R)-[¹⁸F]FMA in 10⁵ CFUs S. aureus-inoculated mice showed high uptake of tracer at the site of live bacterial inoculation compared with that of heat-killed bacterial inoculation (FIG.18). The ratio of in vivo (SUV) and ex vivo (%IDg^-1) PET signals in 10⁵ CFUs inoculated mice was decreased compared with that calculated for 10⁶ CFUs inoculated mice, but differences were still significant (In vivo: 3.30 ± 1.20; P = 0.0260, Ex vivo: 2.72 ± 0.70; P = 0.0119). In contrast, iPET/CT images of (R)-[¹⁸F]FMA in 10⁴ CFUs S. aureus inoculated mice did not provide visible signals without differences between live and heat-killed inoculations (SUV ratio: 1.10 ± 0.13; P = 0.6951, %IDg^-1 ratio: 1.54 ± 0.48; P = 0.0867). See FIG.19. _{[0154] In summary, the 18F-labeled N-acetyl muramic acid derivatives (S)- and (R)-[18F]FMA} were synthesized via a simple acylation approach from commercially available muramic acid. Both (S)- and (R)-[¹⁸F]FMA showed excellent performance both in vitro and in vivo with marked accumulation by several clinically relevant pathogens, including S. aureus. Without being bound by theory, it is believed that the differences in (S)-and (R)-[¹⁸F]FMA by several pathogens may relate to the subtle structural requirements of peptidoglycan biosynthesis. E^XAMPLE 5 Synthesis of compounds of Formula (II), Formula (IIa), and Formula (IV) _{[0155] Compounds of Formula (II), Formula (IIa), and Formula (IV) are prepared from} commercially available anhydro muramic acid. Anhydro muramic acid (“anhydro muramic acid- OH”) is optionally esterified (e.g., to “anhydro muramic acid-OMe”) using methods known to the skilled artisan, including those shown in the following scheme (i.e., as described in Brown et al., ACS Chem. Biol.2021, 16, 1908-1916 and Supporting Information).

Attorney Docket: 048536-772001WO _{[0156] Acylation of anhydro muramic acid-OH or anhydro muramic acid-OMe, e.g., by} reacting anhydro muramic acid-OH or anhydro muramic acid-OMe with an ¹⁸F-labeled activated ester, yields the compound of Formula (II), (IIa), or (IV), as shown in the following scheme, wherein R^x, R¹, R², and R³ are as defined for Formula (II) or (IIa) or (IV).

Synthesis of Additional Compounds of Formula (I), and of Formula (III) and (IIIa) _{[0157] Compounds of Formula (I), Formula (III), and Formula (IIIa) are prepared from} commercially available muramic acid (“muramic acid-OH”). Esterified muramic acid (e.g., “muramic acid-OMe”) is synthesized using methods known to the skilled artisan, including from commercially available glucosamine (i.e., as described in Brown et al., ACS Chem. Biol.2021, 16, 1908-1916 and Supporting Information). Attorney Docket: 048536-772001WO

_{[0158] Acylation of muramic acid-OH or muramic acid-OMe, e.g., by reacting anhydro} muramic acid-OH or anhydro muramic acid-OMe with an ¹⁸F-labeled activated ester, yields the compound of Formula (I) or Formula (III) or (IIIa), as shown in the following scheme, wherein R^x, R¹, R², and R³ are as defined for Formula (I) or (III).

Synthesis of activated ester intermediates _{[0159] The 18F or 19F activated ester reagents used in Examples 5 and 6 (e.g., as provided in} Krishnan et al., Chemistry, 2017, 23(62): 15553-15577), are prepared according to methods Attorney Docket: 048536-772001WO known to the skilled artisan (e.g., as described in Kim et al., RSC Adv., 2019, 9, 32175-32183; or Li et al., Nuclear Medicine and Biology, 2020, 90-91: 84-89) and as shown any of the following schemes, wherein: Phase transfer catalyst (PTC) is K222 or 18-C-6 or TBAHCO3, TEAHCO3; and Base is K₂CO₃, KHCO₃, Cs₂CO₃, CsHCO₃; (e.g.: 1. K₂₂₂/K¹⁸F or K¹⁹F; 2. K₂₂₂/Cs¹⁸F or Cs¹⁹F; 3.18-C-6/K¹⁸F or K¹⁹F; 4.18-C-6/Cs¹⁸F or Cs¹⁹F; 5. K¹⁸F or K¹⁹F; 6. Cs¹⁸F or Cs¹⁹F; 7. TBAHCO3 or TEAHCO3); Solvent is acetonitrile, DMF, tBuOH/MeCN, or 5-amyl alcohol; Temperature is 80 to 140 °C; and Time is 5 to 30 minutes. p-Nitrophenyl esters

Attorney Docket: 048536-772001WO

NHS esters and Tetrafluorophenyl esters

Claims

Attorney Docket: 048536-772001WO CLAIMS WHAT IS CLAIMED IS: 1_{. A compound having the structure of Formula (I)} , or a pharmaceutically acceptable

R¹ is ¹⁸F; R² is H, D, ¹⁹F, or unsubstituted C1-C5 alkyl; R³ is H, D, ¹⁹F, or unsubstituted C1-C5 alkyl; and R^x is H, methyl, or ethyl. 2. The compound of claim 1, wherein the compound has the structure of Formula (Ia) , or a pharmaceutically acceptable

3. The compound of claim 1 or 2, wherein: R² is H, D, ¹⁹F, or methyl; and R³ is H, D, ¹⁹F, or methyl. 4. The compound of any one of claims 1-3, wherein the compound is selected from the group consisting of: Attorney Docket: 048536-772001WO ,

5. The compound of claim 4, wherein the compound is selected from the group consisting of:

or a pharmaceutically acceptable salt thereof. 6. The compound of any one of claims 1-5, wherein R^x is H. 7. The compound of any one of claims 1-5, wherein R^x is methyl. 8. A compound having the structure of Formula (II) Attorney Docket: 048536-772001WO

or a pharmaceutically acceptable salt thereof, wherein: R¹ is ¹⁸F; R² is H, D, ¹⁹F, or unsubstituted C1-C5 alkyl; R³ is H, D, ¹⁹F, or unsubstituted C₁-C₅ alkyl; and R^x is H, methyl, or ethyl. 9. The compound of claim 8, wherein the compound has the structure of Formula (IIa) .

10. The compound of claim 8 or 9, wherein: R² is H, D, ¹⁹F, or methyl; and R³ is H, D, ¹⁹F, or methyl. 11. The compound of any one of claims 8-10, wherein the compound is selected from the group consisting of: , or a

Attorney Docket: 048536-772001WO 12. The compound of any one of claims 8-11, wherein R^x is H. 13. The compound of any one of claims 8-11, wherein R^x is methyl. 14. A pharmaceutical composition comprising a compound of any one of claims 1-13, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient. 15. A method of detecting bacteria in a subject, comprising (i) administering an effective amount of an imaging agent comprising an ¹⁸F label to the subject; (ii) allowing the bacteria in the subject to incorporate the ¹⁸F label intracellularly, or into the bacterial cell wall of the bacteria, thereby forming an ¹⁸F labeled bacteria; and (iii) detecting the ¹⁸F labeled bacteria in the subject, wherein the imaging agent comprising an ¹⁸F label is a compound of any one of claims 1-13, or a pharmaceutically acceptable salt thereof. 16. The method of claim 15, wherein step (ii) comprises allowing the bacteria in the subject to incorporate the ¹⁸F label intracellularly into the periplasmic space of the bacteria. 17. The method of claim 15 or 16, wherein the imaging agent comprising an ¹⁸F label is selected from the group consisting of: , or a

18. The method of any one of claims 15-17, wherein detecting the ¹⁸F labeled bacteria in the subject, comprises performing a PET scan of the subject. Attorney Docket: 048536-772001WO 19. The method of any one of claims 15-18, wherein administering an effective amount of an imaging agent comprising an ¹⁸F label to the subject comprises intravenous injection of the imaging agent comprising an ¹⁸F label. 20. The method of any one of claims 15-19, wherein the method further comprises: (iv) selecting a therapeutic agent for treating the bacteria in the subject; (v) administering the therapeutic agent to the subject; (vi) allowing the bacteria in the subject to respond to the therapeutic agent; and (vii) monitoring the therapeutic effect of the therapeutic agent. 21. The method of claim 20, wherein monitoring the therapeutic effect of the therapeutic agent comprises (vii-1) administering an effective amount of the imaging agent comprising an ¹⁸F label to the subject; (vii-2) allowing the bacteria in the subject to incorporate the ¹⁸F label intracellularly, into the bacterial cell wall, or into the periplasmic space of the bacteria, thereby forming ¹⁸F labeled bacteria; (vii-3) detecting the ¹⁸F label, thereby detecting the bacteria in the subject; and (vii-4) identifying a change from the detection from step (iii) to the detection from step (vii-3). 22. The method of claim 20 or 21, wherein the therapeutic agent is an antibiotic. 23. A compound having the structure of Formula (III) OH O OH O , or a pharmaceutically

Attorney Docket: 048536-772001WO R¹ is ¹⁸F; and R^x is H, methyl, or ethyl. 24. The compound of claim 23, having the structure of Formula (IIIa) or a pharmaceutically

25. The compound of claim 23, wherein the compound is: , or a

26. A compound having the structure of Formula (IV) , or a pharmaceutically R¹ is ¹⁸F; and

R^x is H, methyl, or ethyl.