[go: up one dir, main page]

WO2018148367A1 - Résine de piégeage d'azide - Google Patents

Résine de piégeage d'azide Download PDF

Info

Publication number
WO2018148367A1
WO2018148367A1 PCT/US2018/017357 US2018017357W WO2018148367A1 WO 2018148367 A1 WO2018148367 A1 WO 2018148367A1 US 2018017357 W US2018017357 W US 2018017357W WO 2018148367 A1 WO2018148367 A1 WO 2018148367A1
Authority
WO
WIPO (PCT)
Prior art keywords
reaction
azide
composition
solid support
alkyne
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2018/017357
Other languages
English (en)
Inventor
Steven W. Millward
Stephen V. FIACCO
Federica Pisaneschi
David Piwnica-Worms
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Evorx Technologies Inc
MD Anderson Cancer Center
Original Assignee
Evorx Technologies Inc
MD Anderson Cancer Center
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Evorx Technologies Inc, MD Anderson Cancer Center filed Critical Evorx Technologies Inc
Publication of WO2018148367A1 publication Critical patent/WO2018148367A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/22—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising organic material
    • B01J20/26—Synthetic macromolecular compounds
    • B01J20/265—Synthetic macromolecular compounds modified or post-treated polymers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A61K51/04—Organic compounds
    • A61K51/041—Heterocyclic compounds
    • A61K51/044—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins
    • A61K51/0446—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine, rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
    • A61K51/04—Organic compounds
    • A61K51/08—Peptides, e.g. proteins, carriers being peptides, polyamino acids, proteins
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/281—Sorbents specially adapted for preparative, analytical or investigative chromatography
    • B01J20/282—Porous sorbents
    • B01J20/285—Porous sorbents based on polymers
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/11—Compounds covalently bound to a solid support

Definitions

  • This invention relates to chemical labeling procedures, and more specifically to an azide resin-based system, use of which results in compounds with increased specific activities.
  • the copper catalyzed azide-alkyne cycloaddition reaction is a versatile example of "click chemistry” owing mainly to its high yield, chemical orthogonality, water compatibility, and rapid kinetics (Kolb et al. (2001 ) Angew. Chem. In. Ed. 40:2004-2021 ).
  • Click chemistry has found extensive use in the field of fluorine-18 academic radiochemistry where fast reaction kinetics, high yields, and mild reaction conditions are highly desirable.
  • fluorine-18 click chemistry involves the radiosynthesis of the prosthetic group [ 18 F]fluoroethylazide (FEA) followed by its distillation and subsequent reaction with an alkyne precursor (mainly small molecules or peptides).
  • the specific activity for a radiopharmaceutical is a measurement of radioactivity per mass of cold pharmaceutical. For fluorine-18-labeled radiopharmaceuticals, this often becomes a measurement of any co-eluting cold impurity, particularly the precursor compound, which often competes with the radiopharmaceutical for binding to the biological target. This value is also referred to as apparent specific activity, usually expressed in GBq/ ⁇ , and it is particularly relevant when the imaging target is a saturatable system, such as a cell surface receptor.
  • This metric takes on additional importance when the radiopharmaceutical is synthesized by prosthetic group radiochemistry (e.g., fluoroethylazide), where the difference in structure between precursor and labeled species is subtle and the prosthetic group lies outside the binding site of the target.
  • prosthetic group radiochemistry e.g., fluoroethylazide
  • Low apparent specific activities therefore, can result in poor tracer uptake and low signal-to-noise in tissues that express the target of interest.
  • chromatography also introduces additives and solvents (e.g., acetonitrile, TFA) which must be removed in subsequent steps and specifically accounted for during product quality control and Good Manufacturing Practice (GMP) production.
  • additives and solvents e.g., acetonitrile, TFA
  • [ 18 F]fluoroethylazide labeling of 4 different alkynes ranging from ⁇ 300 Da to > 1700 Da has been carried out in which 98% of the unreacted alkyne was removed in less than 20 minutes at room temperature to afford the final radiotracers in > 99% radiochemical purity with specific activities up to > 200 GBq/ ⁇ .
  • This methodology has been applied to label a novel cyclic peptide (previously shown to bind the Her2 receptor with high affinity) and demonstrated tumor-specific uptake and low nonspecific background by PET/CT.
  • This methodology is automated, rapid, mild, and general allowing peptide-based fluorine-18 radiotracers to be obtained with clinically-relevant specific activities without chromatographic separation within currently standard total synthesis times.
  • the present disclosure provides a azide-functionalized solid support for removing the unreacted alkynes from an azide-alkyne click radiolabeling reaction for 18 F radioradiotracers.
  • the solid support is a polymer resin.
  • the solid support is a TentaGelTM resin.
  • the azide-alkyne click radiolabeling reaction is a
  • the alkynes can be strained alkynes or terminal alkynes.
  • one or more azidoacetic acid groups are conjugated with each amine in the underivatized resin. Multiplying the equivalents of azide on the polymer resin results in improved stripping efficiency of the conjugated resin.
  • the alkynes can be strained alkynes or terminal alkynes.
  • one or more azidoacetic acid groups are conjugated with each amine in the underivatized resin. Multiplying the equivalents of azide on the polymer resin results in improved stripping efficiency of the conjugated resin.
  • radiolabeling reaction can be manual or automated.
  • an automated radiolabeling reaction can be performed on commercially available platforms such as, but not limited to, GE Tracerlab and NanoTek automated devices. These devices utilize a stripping resin module, where the composition of the present invention can be incorporated into a cartridge within the automated hands-free workflow system.
  • the invention relates to an industrial process for radiolabeling incorporating an azide-functionalized resin, where the process includes a solid or semi-solid support for removing unreacted alkynes from an azide-alkyne click radiolabeling reaction for 18 F radioradiotracers.
  • the present disclosure provides a method of producing an azide-functionalized solid support, wherein the solid support can be used to remove the unreacted alkynes from an azide-alkyne click radiolabeling reaction for 18 F radioradiotracers.
  • the present disclosure provides a method of improving the specific activity of radiolabel compound, wherein an azide- functionalized solid support is used to remove unreacted alkyne precursors from a [ 18 F]fluoro radiolabeling reaction.
  • the present disclosure provides a method of enhancing the specific activity of [ 18 F]fluoroethylazide -labeled biologies comprising affibodies, fibronectin-based affinity agents, single-chain variable fragment (ScFv), antigen-binding (Fab) fragment, and antibodies.
  • the proposed method in the disclosure can be applied to the removal of alkynes from process scale reactions, which can be useful in the petrochemical industry where eliminating alkynes from a feedstock or process line is desirable.
  • the disclosed method can be used to enrich a click reaction product.
  • This reaction product may be difficult to purify or isolate from the unreacted precursors when the reaction is conducted using standard azide- functionalized chemicals without a solid support.
  • Figure 1 A is a general schematic representation of the synthesis of an azide-functionalized solid support according to one aspect of the present disclosure
  • Figure 1 B is a general schematic representation of scavenging unreacted alkynes using the azide-functionalized solid support according to one aspect of the present disclosure
  • Figure 2A is a schematic representation of the synthesis of an azide resin according to the disclosure.
  • Figure 2B is a schematic representation of [ 18 F] fluoroethylazide labeling and scavenging during radiosynthesis of compound [ 18 F]1 ;
  • Figure 3 is a graphic representation of the stability of an azide resin according to the disclosure at 4 °C;
  • Figure 4 is a set of schematic representations of the [ 18 F]-labeled compounds synthesized: [ 18 F]1 , [ 18 F]2, [ 18 F]3, and [ 18 F]4 and [ 18 F]-SUPR4;
  • Figure 5 is a set of radio-HPLC scans of [ 18 F]1 -/; [ 18 F]1 -UV 220 , 1 (alklyine precursor-UV 2 2o, and [ 18 F] UV220 using gradient A;
  • Figure 6 is a set of radio-HPLC scans of [ 18 F ]2- [ 18 F]2-UV 220 2 (alklyine precursor- UV220, and [ 19 F]-2 UV220 using gradient B;
  • Figure 7 is a set of radio-HPLC scans of [ 18 F]3-y " , [ 18 F]3- UV 220 and 3 (alklyine precursor- UV220, using gradient C;
  • Figure 8A is a set of radio-HPLC scans of [ 18 F]-SUPR4-y " , [ 18 F]-SUPR- UV220, [ 19 F]-SUPR-UV 220 , using gradient D;
  • Figure 8B is a set of radio-HPLC scans of [ 18 F]-SUPR4-y " , [ 18 F]SUPR- UV220, [ 19 F]-SUPR- UV220, using gradient E;
  • Figure 9A is a set of radio-HPLC scans of the synthesis of [ 18 F]-SUPR;
  • Figure 9B is a graphic representation of cell lines with varying levels of Her2 expression (BT474 and SKOV3 (shCTRL);
  • Figure 9C is a graphic representation of in vitro binding of SKOV
  • Figure 10A is a set of representations of PET/CT scans of axial (Ax), coronal (Cor), and Sagittal (Sag) slices of mice with a Her2-positive SKOV3 subcutaneous tumor which had been treated with [ 18 F]-SUPR4;
  • Figure 10B is a set of PET/CT scans of mouse slices with a SKOV3 (R) or MDA-MB-231 (L) tumor labeled with [ 18 F]-SUPR4;
  • Figure 10C is a graphic representation of the Standard Uptake Values (SUVmean) for each tumor and contralateral muscle obtained from PET/CT images and used to calculate the tumormuscle ratio of [ 18 F]-SUPR4 uptake in the SKOV3 and MD-MB-231 mouse models; and
  • Figure 10D is a set of radio-HPLC scans of mouse plasma collected 1 hour post-injection of [ 18 F]-SUPR4. DESCRIPTION
  • An azide-derivatized solid support acts as an efficient scavenger of unreacted alkynes in the click labeling reaction and eliminate the need for HPLC purification.
  • a "solid" support is a general term that is intended to include semi-solid and gel forms, as well as colloids.
  • the azide resin removes > 98% of the unreacted alkyne precursors in under 20 minutes at room temperature.
  • the final 18 F-labeled products were determined to have specific activities between 12 GBq/ ⁇ to 222 GBq/ ⁇ and radiochemical purities > 99%.
  • FIG. 1 A A general representation of the synthetic route to an azide-functionalized solid support is shown in Fig. 1 A.
  • the azide functional groups are used to modify the solid support surface, which enable the solid support to efficiently react with alkyne molecules and act as an alkyne scanvenger.
  • This scanvenging process is shown in Fig. 1 B, which removes unreacted alkynes in a 18 F-labeling reaction.
  • the PEGylated TentaGelTM resin was selected as the solid support because of its biocompatibility as well as its hydrophilicity and ease of chemical modification. Reaction of amine-derivatized TentaGelTM (TentaGelTM-NH 2 ) with 2- azidoacetic acid (Fig. 2A) resulted in a highly derivatized resin with up to 96% of the reactive amines capped. The resin was found to be highly stable and can be stored up to 6 months at 4 °C in DMF with only 3% loss of reactivity (Fig. 3).
  • radiosyntheses involve the automated production of [ 18 F]FEA, the click step is often carried out manually.
  • the entire radiosynthesis of [ 18 F]FEA and subsequent click step was implemented on the automated module GE TracerLabTM where the scavenging unit can be incorporated as part of the purification work-flow in between the click labeling step and the final formulation unit.
  • [ 18 F]fluoride was trapped into a QMA cartridge, released and dried in the presence of K 2 C0 3 and Kryptofix 2,2,2. Production of the prosthetic group [ 18 F]FEA from tosylethylazide occurred in the TracerLabTM main reactor in 15 minutes at 80 °C, followed by distillation of
  • the stripping reaction was allowed to proceed at room temperature with nitrogen agitation followed by dilution into 0.085% NaH 2 P0 4 , purification on a C18 cartridge, and elution with PBS:EtOH for injection.
  • the total synthesis time is approximately 80 minutes.
  • SUPR4 a cyclic peptide containing unnatural amino acids (N- methyl norvaline) previously selected for binding to the Her2 receptor by mRNA display.
  • SUPR4 was shown to have mid-nanomolar affinity for the Her2 receptor, rapid renal clearance from circulation, and high Her2-dependent tumor uptake by near-infrared (NIR) optical imaging.
  • NIR near-infrared
  • FIGs. 10A - 10C In addition to uptake in the tumor, significant signal was observed in the gallbladder and kidneys consistent with rapid renal clearance with minor hepatobiliary excretion.
  • Post-imaging analysis of tumormuscle (T:M) uptake ratios showed a modest but statistically significant increase in SKOV3 tumors relative to MDA-MB-231 tumors which showed the expected T:M of 1 indicating no specific probe uptake in the absence of the Her2 receptor (Fig. 10C).
  • Serum analysis by radio-HPLC at 1 hour post-injection showed > 98% of the radiotracer was intact by comparison to an uninjected sample of the radiotracer, again in agreement with previous in vitro serum stability analysis (Fig. 10D).
  • Buffer A dH 2 0 with 0.1 % (v/v) TFA
  • Buffer B CH 3 CN + 0.1 % (v/v)
  • reaction was mixed with ethyl acetate (10 mL) and the organic phase washed twice with 1 N HCI, twice with saturated NaHC0 3 and twice with brine. The organic phase was dried over MgS0 4 . After filtration of the salts and evaporation under vacuum, the remaining amber oil was dissolved in a 1 : 1 mixture of CH 3 CN:DMF (300 ⁇ _). To this were added CuS0 4 (8 mg) and L-ascorbic acid (15 mg) in of H 2 0 (500 ⁇ _), followed by 100 mM TBTA (2 ⁇ _) and then 0.2 M 2-fluoroethylazide (500 ⁇ _).
  • Peptide Synthesis [0054] Peptides were synthesized using an automated peptide synthesizer (Biotage Alstra). Rink Amide MBHA (364 mg, 0.55 ⁇ /g, P3 Bio) was swelled in DMF for 10 min, heated to 65 °C followed by washing with DMF.
  • Fluorenylmethyloxycarbonyl chloride (FMOC) deprotections were performed using two successive reactions at 50 °C for 3 min in 20% 4-Methylpiperidine in DMF. Amino acid couplings were carried out at 65 °C for 7 min using 5 equivalents of amino acid delivered at 0.4 M, 5 equivalents of 1 -[Bis(dimethylamino)methylene]- 1 H-1 ,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (HATU) delivered at 0.5 M and 10 equivalents 4-methylmorpholine (NMM) delivered at 2 M.
  • HATU 1-[Bis(dimethylamino)methylene]- 1 H-1 ,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate
  • NMM 4-methylmorpholine
  • the N-terminus was capped with 15 equivalents of glutaric anhydride delivered at 0.4 M and 30 equivalents NMM delivered at 2 M for 7 min at 65 °C.
  • the C-terminal MTT-protected Lysine was deprotected by washing with DCM followed by 30 min of continuous washing with 5% TFA and 1 % Triisopropylsilane (TIS) in DCM followed by neutralization of the acid with successive washes of DCM, DMF, 10% NMM in DMF and DMF.
  • TFA Triisopropylsilane
  • the crude product was purified on a Vydac C-18 reverse phase HPLC column using gradient elution (20% Buffer B for 5 min, 20% to 70% Buffer B over 35 min; Buffer A: dH 2 0 with 0.1 % (v/v) TFA, Buffer B: CH 3 CN + 0.1 % (v/v) TFA). Lyophilized peptide was
  • a 120 mM solution of alkyne precursor in DMSO (5 ⁇ , 600 nM) was added to a solution of 180 mM 2-fluoroethylazide in DMF (100 ⁇ _, 18 ⁇ , 30 equivalents) along with a 100 mM TBTA in DMF (8 ⁇ _, 720 nM), CuS0 4 /ascorbic acid solution in dH 2 0 (100 ⁇ _, 64 mM CuS0 4 , 340 mM Ascorbic acid), and CH 3 CN (140 ⁇ ).
  • the reaction was purified on a Vydac C-18 reverse phase HPLC column using gradient elution (25% Buffer B for 5 min, 25% to 75% Buffer B over 35 min; Buffer A: dH 2 0 with 0.1 % (v/v) TFA, Buffer B: ACN + 0.1 % (v/v) TFA). Dried peptide was reconstituted in DMSO and quantitated by
  • SUPR4-Cys (3 mg) dissolved in DMSO (250 ⁇ _) and 1 ,4,7,10- Tetraazacyclododecane-1 ,4,7-tris-acetic acid-10-maleimidoethylacetamide (3.9 mg, 3 equivalents) dissolved in DMF (250 ⁇ _) were added to Phosphate Buffer (500 ⁇ _, pH 7.5) and end-over-end rotated at RT for 2+ hr.
  • Phosphate Buffer 500 ⁇ _, pH 7.5
  • Radiosyntheses were performed on TracerLabTM FX (General Electric Healthcare, Munster, Germany) automatic module.
  • [ 18 F]Fluoride was obtained as an aqueous solution from the MD Anderson Cyclotron Radiochemical Facility (CRF).
  • [ 18 F]Fluoride was adsorbed on an ion exchange cartridge (Pre-conditioned Sep-PAK® Light QMA Cartridge, ABX GmbH, Radeberg, Germany).
  • [ 18 F]Fluoride was flushed into the reaction vial with a potassium carbonate and Kryptofix 2.2.2.
  • water/CH 3 CN solution 700 ⁇ _; 52.8 mg K 2 C0 3 , 240.1 mg K 222 , 4 mL water, 16 mL CH 3 CN).
  • the solution was dried under vacuum and under nitrogen flow at 60 °C for 2 min. 500 ⁇ dry CH 3 CN was added and then the mixture was azeotropically dried at 120 °C for additional 3 min.
  • the mixture was transferred into a plastic solid phase scavenging reactor containing the azide resin (800 ⁇ _; 80 mg/mL) pre-swollen in DMF, washed with a CuS0 4 and sodium ascorbate mixture (200 ⁇ ), and loaded with CuS0 4 (50 ⁇ ; 35 mg/mL in water), sodium ascorbate (50 ⁇ ; 174 mg/mL in PBS), TBTA (13 ⁇ ;
  • BT474 cells were grown in DMEM/F-12 (50/50) with 3.6 ⁇ g/mL human insulin (Sigma), 10% fetal bovine serum (FBS) and 1 %
  • SKOV3 shRNA control (shCTRL) and shRNA Her2 knockdown (shHER2) cell lines were generated by the University of Texas MD Anderson Cancer Center shRNA & ORFeome Core Facility using Dharmacon GIPZ lentiviral shRNAs (Genecode V3LHS/635339) according to manufacturer protocols.
  • SKOV3 shCTRL and SKOV3 shHER2 were maintained using McCoy's 5A media supplemented with 10% FBS, 1 % PS and 2-3 ⁇ g/mL puromycin.
  • mice were subcutaneously injected with 1 .5 x 10 6 SKOV3 or MDA-MB-231 cells near the shoulder. After 8 wk to 10 wk, mice were intravenously injected with 100 ⁇ of [ 18 F]-SUPR4 via the tail vein.
  • PET/CT images were acquired 1 hr post injection on a Bruker Albira PET/CT/SPECT Preclinical Imaging System and iteratively reconstructed using an iterative MLEM algorithm. PET/CT data was analyzed and quantitated using PMOD v3.505 software.
  • Volumes of interest were drawn manually on CT images and used to calculate SUV, %ID/g, and tumor-to- muscle ratios on corresponding registered PET images.
  • Statistical analysis was performed using unpaired t-tests in Graphpad Prism 6. Representative images were generated using the Siemens Inveon Research Workplaces v4.2 software package.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Medicinal Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Optics & Photonics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

L'invention concerne une résine d'azide à base de TentaGelc ™ qui est capable d'éliminer rapidement le précurseur d'alcyne n'ayant pas réagi dans des réactions de radiomarquage de fluoroéthylazide [18F] conduisant à des activités spécifiques considérablement accrues.
PCT/US2018/017357 2017-02-08 2018-02-08 Résine de piégeage d'azide Ceased WO2018148367A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201762456169P 2017-02-08 2017-02-08
US62/456,169 2017-02-08

Publications (1)

Publication Number Publication Date
WO2018148367A1 true WO2018148367A1 (fr) 2018-08-16

Family

ID=63107016

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2018/017357 Ceased WO2018148367A1 (fr) 2017-02-08 2018-02-08 Résine de piégeage d'azide

Country Status (1)

Country Link
WO (1) WO2018148367A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2025150713A1 (fr) * 2024-01-11 2025-07-17 서울대학교산학협력단 Nano-plateforme d'albumine à surface modifiée, son procédé de préparation et composition pour le diagnostic ou le traitement d'une maladie utilisant celle-ci

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012134925A1 (fr) * 2011-03-25 2012-10-04 Life Technologies Corporation Esters hétérobifonctionnels à utiliser dans marquage de molécules cibles

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012134925A1 (fr) * 2011-03-25 2012-10-04 Life Technologies Corporation Esters hétérobifonctionnels à utiliser dans marquage de molécules cibles

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
KETTENBACH, K. ET AL.: "18F-Labeling Using Click Cycloadditions", BIOMED RESEARCH INTERNATIONAL, vol. 2014, 2014, pages 1 - 16, XP055537307 *
LEEB, L. ET AL.: "Optimization of Click Chemistry Using Azide and Alkyne Scavenger Resins", QSAR & COMBINATORIAL SCIENCE, vol. 26, no. 11-12, 2007, pages 1145 - 1150, XP055537301 *
PISANESCHI, F. ET AL.: "Automated, Resin-Based Method to Enhance the Specific Activity of Fluorine-18 Clicked PET Radiotracers", BIOCONJUGATE CHEMISTRY, vol. 28, no. 2, 2 February 2017 (2017-02-02), pages 583 - 589, XP055537297 *
SIRION, U. ET AL.: "Azide/Alkyne Resins for Quick Preparation of 1,4-Disubstituted 1,2,3-Triazoles", BULLETIN OF THE KOREAN CHEMICAL SOCIETY, vol. 31, no. 7, 2010, pages 1843 - 1847 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2025150713A1 (fr) * 2024-01-11 2025-07-17 서울대학교산학협력단 Nano-plateforme d'albumine à surface modifiée, son procédé de préparation et composition pour le diagnostic ou le traitement d'une maladie utilisant celle-ci

Similar Documents

Publication Publication Date Title
Namavari et al. A novel method for direct site-specific radiolabeling of peptides using [18F] FDG
Meyer et al. Exploring structural parameters for pretargeting radioligand optimization
Li et al. Oxime formation for fluorine-18 labeling of peptides and proteins for positron emission tomography (PET) imaging: A review
Ait-Mohand et al. Evaluation of 64Cu-labeled bifunctional chelate–bombesin conjugates
Prante et al. 3, 4, 6-Tri-O-acetyl-2-deoxy-2-[18F] fluoroglucopyranosyl phenylthiosulfonate: a thiol-reactive agent for the chemoselective 18F-glycosylation of peptides
Kettenbach et al. 18F‐labeling using click cycloadditions
Litau et al. Next Generation of SiFA lin-Based TATE Derivatives for PET Imaging of SSTR-Positive Tumors: Influence of Molecular Design on In Vitro SSTR Binding and In Vivo Pharmacokinetics
EP2680889B1 (fr) Analogues d'octréotate radiomarqués comme indicateurs pour tep
Billaud et al. Pretargeted PET imaging using a bioorthogonal 18F-labeled trans-cyclooctene in an ovarian carcinoma model
Kasten et al. Clickable, hydrophilic ligand for fac-[MI (CO) 3]+(M= Re/99mTc) applied in an S-functionalized α-MSH peptide
Liu et al. 18F-Trifluoroborate derivatives of [des-Arg10] kallidin for imaging bradykinin B1 receptor expression with positron emission tomography
Knight et al. Synthesis and evaluation of an 18 F-labelled norbornene derivative for copper-free click chemistry reactions
Maschauer et al. 18F-and 68Ga-labeled neurotensin peptides for PET imaging of neurotensin receptor 1
Alshoukr et al. Novel DOTA-neurotensin analogues for 111In scintigraphy and 68Ga PET imaging of neurotensin receptor-positive tumors
CN113677400A (zh) 结合psma的双模式放射性示踪剂及治疗剂
Kuchar et al. Site-selective radiolabeling of peptides by 18F-fluorobenzoylation with [18F] SFB in solution and on solid phase: a comparative study
Grob et al. Design of radiolabeled analogs of minigastrin by multiple amide-to-triazole substitutions
Leier et al. Radiometal-containing aryl diazonium salts for chemoselective bioconjugation of tyrosine residues
Wester et al. Fluorine-18 labeling of peptides and proteins
Rosik et al. Incorporation of a triglutamyl spacer improves the biodistribution of synthetic affibody molecules radiofluorinated at the N-terminus via oxime formation with 18F-4-fluorobenzaldehyde
WO2016054277A1 (fr) Ligands de cycloadditions d'azide-alcyne catalysées par cu(i) (cuaac) et procédés de conduite de réactions de cycloaddition d'azide-alcyne catalysée par cu(i)
Narayanam et al. Positron emission tomography tracer design of targeted synthetic peptides via 18F-sydnone alkyne cycloaddition
Raheem et al. Ultrasonic-Assisted Solid-Phase Peptide Synthesis of DOTA-TATE and DOTA-linker-TATE Derivatives as a Simple and Low-Cost Method for the Facile Synthesis of Chelator–Peptide Conjugates
Zhang et al. Radiolabeled B9958 derivatives for imaging bradykinin B1 receptor expression with positron emission tomography: effect of the radiolabel–chelator complex on biodistribution and tumor uptake
Kim Bioorthogonal click chemistry for fluorine-18 labeling protocols under physiologically friendly reaction condition

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 18751747

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 18751747

Country of ref document: EP

Kind code of ref document: A1