Details

Autor(en) / Beteiligte

• Qu, Wenchao
• Kelly, James
• Amor-Coarasa, Alejandro
• waterhouse, Nicole
• Dooley, Marybeth
• Babich, John

Titel

Improved Two-Step Click Synthesis of [^sup 18^F]RPS-040: A Prostate Specific Membrane Antigen (PSMA)-Targeted Tracer for Imaging Prostate Cancer (PCa) Using Positron Emission Tomography (PET)

Ist Teil von

• The Journal of nuclear medicine (1978), 2018-05, Vol.59, p.403

Ort / Verlag

New York: Society of Nuclear Medicine

Erscheinungsjahr

2018

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Objectives: Recently, a high affinity fluorine-18-labeled Glu-urea-Lys-based inhibitor of PSMA, [18F]RPS-040, was developed in our laboratory as a promising PSMA-target radiotracer for imaging prostate cancer by PET (J. Kelly et al). Relying on a 2-[18F]fluoroethylazide/Cu(I)-catalyzed click chemistry methodology, [18F]RPS-040 was synthesized in 105 min with decay-corrected radiochemical yield (dcRCY) of 20 - 40% and radiochemical purity (RCP) greater than 99%. In this research, we aimed to optimize the synthesis and develop a robust method in order to pave the way for translating this promising radiotracer to clinical PCa imaging studies. Methods: [18F]RPS-040 was synthesized using the 2-[18F]fluoroethylazide prosthetic group and Cu(I)-catalyzed click chemistry. The prosthetic group was synthesized from 2-azidoethyltosylate using no-carrier-added [18F]fluoride and TBAHCO3/t-BuOH/CH3CN. The effect of reaction parameters including precursor concentration and reaction time was investigated. Following purification of 2-[18F]fluoroethylazide by distillation, the click reaction was undertaken in a mixed solvent system (t-BuOH/CH3CN/H2O/DMF). [18F]RPS-040 was isolated following semi-prep HPLC purification. Results: At the optimal concentration of 2-azidoethyltosylate (20 mg/mL), reaction temperature (85oC) and reaction time (15 min), 2-[18F]fluoroethylazide was obtained in over 95% conversion yield and 84% distillation yield. The conversion of Cu(I)-catalyzed click reaction was over 95% following 10 min heating at 85 oC in the mixed solvent system. Evaporation of low boiling point solvents from reaction mixture under a simple nitrogen stream prior to semi-prep HPLC improved purification yields. Three consecutive batches were prepared in 100 min from 9.4-9.8 GBq [18F]fluoride. 2.6-2.8 GBq [18F]RPS-040 (53.5 ± 1.6 % dcRCY, n = 3) was obtained at end-of-synthesis, RCP was > 99% and there were no detectable chemical impurities. The molar activity of the final product was 320 ± 11 GBq/µmol (n = 3). Conclusions: A robust method was developed for radiosynthesis of the promising prostate cancer imaging agent [18F]RPS-040. Compared to the previously reported method, modifications in solvent and phase transfer catalyst in radiofluorination step not only improved the yields of the radiofluorination and distillation of the radioactive intermediate but also dramatically increased the yield of the click reaction. Three productions under GMP-compliant conditions provided injectable solutions of [18F]RPS-040 suitable for clinical studies.