A fast, simple, and reproducible automated synthesis of [¹⁸F]FPyKYNE‐c(RGDyK) for α_vβ₃ receptor positron emission tomography imaging

Abstract

18 F]FPyKYNE-c(RGDyK) was successfully synthesized by the Cu(I) catalyzed Huisgen 1,3-dipolar cycloaddition of alkynes to azides using [ 18 F]FPyKYNE as a prosthetic group in an overall radiochemical yield of 12%-18% (decay-corrected) and >99.5% chemical and radiochemical purities in 125 min including quality control. This simple, fully automated two-step, two-reactor approach consists of a quick and convenient purification of the prosthetic group using silica gel cartridges and its subsequent use for the labeling of the azido-c(RGDyK) peptide via click chemistry.

Automated Synthesis of Fluorine-18 Labeled CXCR4 Ligand via the Conjugation with Nicotinic Acid N-Hydroxysuccinimide Ester (6-[18F]SFPy)

“…Although there are a few examples of direct fluorine-18 labeling of peptides, labeling is typically performed using an indirect method [ 39 , 40 , 41 , 42 ]. Therefore, a fully automated synthesis is challenging due to the complexity of the indirect labeling method [ 43 , 44 , 45 , 46 , 47 ]. The steps involved for the preparation of fluorine-18 labeled prosthetic group via currently developed Sep-Pak method (catching of fluorine-18 on an anion exchange cartridge, drying of the cartridge, release of fluorine-18 with precursor), are equivalent to the initial processing of fluorine-18 for conventional nucleophilic fluorination (catching of fluorine-18 on an anion exchange cartridge, the release of fluorine-18 with base, azeotropic drying with acetonitrile).…”

Fully automated peptide radiolabeling from [18F]fluoride

“…48 Valdivia et al generated the [ 18 F]F-pyridyl alkyne prosthetic [ 18 F]FPyKYNE and subsequently coupled it to cRGDyK using a TRACERLab FX FN pro module. 59 Following HPLC-purication, the radiolabeled peptide was obtained in 12-18% decay-corrected yields in 125 minutes with high radiochemical purities (>99%) and specic activities (980-2000 Ci mmol À1 ). 59 This report, however, uses copper-mediated prosthetic coupling, which may not be suitable for all applications and due to the reagent's high toxicity additional purication maybe required to ensure copper levels are below the FDA ICH Q3D guidelines.…”

“…59 Following HPLC-purication, the radiolabeled peptide was obtained in 12-18% decay-corrected yields in 125 minutes with high radiochemical purities (>99%) and specic activities (980-2000 Ci mmol À1 ). 59 This report, however, uses copper-mediated prosthetic coupling, which may not be suitable for all applications and due to the reagent's high toxicity additional purication maybe required to ensure copper levels are below the FDA ICH Q3D guidelines. Recently, Inkster et al introduced a thiol-targeted [ 18 F]uoro-2-cyanobenzothiazole prosthetic, which was subsequently coupled to a cysteine-functionalized cRGDfK peptide using a TRACERLab FX FN pro module.…”

Recent Trends in Bioorthogonal Click-Radiolabeling Reactions Using Fluorine-18

“…An automated synthesis procedure was evaluated for [ 18 F]FPyKYNE and the subsequent radiolabeling of an RGD peptide. The labeled peptide was obtained in a total RCY of 12–18% with a RCP > 99% after 125 min in a two-step, two-reactor process [86].…”