Synthesis of an 18F-labeled CP18 peptide as a potential apoptosis biomarker in PET imaging

1430 Objectives To develop a simple and efficient 18F-labeling protocol for producing clinically acceptable 18F-CP18, a triazole containing pentapeptide, designed as a potential caspase-3 substrate biomarker for in vivo imaging of apoptotic cells. Methods CP18 precursor was prepared in 13 steps and CP18 standard was prepared in 16 steps from commercially available materials. The structural identity of standard CP18 and CP18 precursor were confirmed by 1H, 13C, and MS analyses. 19F NMR was additionally used to characterize the standard CP18. Synthesis of 18F-CP18 was accomplished on a Siemens Explora automated synthesis module. Pentyne tosylate was reacted with K18F in MeCN at 110 C followed by distillation of 18F fluoropentyne into a solution of CP-18 azide precursor in the presence of Cu(I) for the click reaction. 18F-CP18 was purified by RP-HPLC. The dose was formulated in sterile EtOH:sodium phosphate for injection. Results 18F-CP18 was produced with yields in between 15%-40% (decay corrected) and with average synthesis times of 93 min (n = 15). The specific activities ranged from 3 to 11 Ci/μmol with radiochemical purities (RCPs) greater than 95%. 18F-CP18 produced using this protocol was free of K222/pyrogens, passed residual solvent analyses for MeCN (≤ 0.4%) and EtOH ( Conclusions 18F-CP18 was prepared on an automated module with good yields, specific activities and acceptable synthesis time. The tracer passed all QC release tests and was shown to have RCPs greater than 95%. 18F-CP18 produced using this protocol is suitable for human imaging