A new lyophilized kit for ¹⁸F radiolabeling of peptides and temperature-sensitive biomolecules

Objectives The aim of this study was to develop a rapid, one step, kit to radiolabel peptides with ¹⁸F, in high yield and/or at high specific activity.

Methods A NODA-MPAA ligand was attached to a peptide for pretargeting (IMP485) and a NOTA ligand was attached to octreotide. 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 ¹⁸F^- in saline/EtOH (400 μL), heating briefly, and then purifying rapidly by solid phase extraction (SPE). The kits were optimized by examining the effects of pH, reaction time, temperature, peptide concentration, different buffers, Al³⁺/peptide ratios, the addition of a co-solvent, and an antioxidant.

Results An optimized kit containing 20 nmol of IMP485 was labeled with ¹⁸F in a single step, with a specific activity up to 222 GBq/μmol (6015 Ci/mmol) in high isolated yield (45-97%) after a simple SPE purification. The total reaction and purification time was about 20 min. Optimal IMP485-kit labeling yields were observed at pH 4.0, stabilized by the nonvolatile buffer, potassium biphthalate. Nearly quantitative radiolabeling yields were obtained with as little as 40 nmol of IMP485. Slightly lower labeling yields were obtained with the NOTA ligand on octreotide, but high specific activities were still achievable and good yields were obtained even at 50^○C.

Conclusions Optimized, facile, lyophilized kits containing peptides conjugated with NOTA/NODA were developed. The peptide kits have been ¹⁸F-labeled at specific activities as high as 222 GBq/μmol (6015 Ci/mmol). This labeling technique appears to be generally useful, since the octreotide and the pretargeting peptide lyophilized kits labeled in good yields with high specific activity. The NOTA-octreotide peptide also labeled well at low temperature, suggesting that direct labeling of some temperature-sensitive compounds may be possible.

Research Support Supported in part by NIH Grant# 5R44RR028018