A facile kit for F-18 radiolabeling of peptides for PET

1489 Objectives The aim of this study was to develop a rapid, one-step, kit to radiolabel peptides with F-18, at high specific activity. Methods A new 2-(4-(carboxymethyl)-7-{[4-(carboxymethyl)phenyl]methyl}-1,4,7-triazacyclononan-1-yl)acetic acid (NODA-MPAA) ligand was attached to peptides for pretargeting and receptor targeting. The peptides were formulated in lyophilized kits containing Al3+, ascorbic acid, and a bulking agent. The peptide kits were radiolabeled in one step by adding F-18 in saline, heating briefly, and then purifying rapidly by solid phase extraction (SPE). The kits were optimized by examining the effects of pH, different bulking agents, Al3+/peptide ratios and the addition of a co-solvent and an antioxidant. Results An optimized kit containing 20 nmol of a NODA-MPAA-peptide for pretargeting was labeled with F-18 in a single step with a specific activity up to 153 GBq/μmol (4135 Ci/mmol) in high isolated yield (58-93%) after a simple SPE purification. The total reaction and purification time was about 30 min. Optimal kit labeling yield was observed at pH 4.0±0.2, with 0.1 mg of ascorbic acid. A 1:1 ratio of F-18 in saline to ethanol was used for the radiolabeling and an Al:NODA-MPAA-peptide ratio was optimal at about 0.6:1. Similar labeling results were obtained with octreotide and bombesin peptides. An acceptable lypohilized cake was prepared using α,α-trehalose as a bulking agent; 2.5% to as much as 50%/wt did not affect the radiolabeling yield. Conclusions An optimized, facile kit containing 20 nmol of a NODA-MPAA-peptide for pretargeting was radiolabeled with F-18 in saline/ethanol 1:1, heated to 100°C briefly and then purified by SPE to produce the F-18-labeled peptide in a single step and in high yield. The peptide kits have been F-18-labeled with specific activities as high as 153 GBq/μmol (4135 Ci/mmol). This labeling technique appears to be generally useful, since the receptor targeting peptide kits labeled with the same efficiency as the pretargeting peptide kit. Research Support Supported in part by NIH Grant# 5R44RR028018