Optimization of hapten-peptide labeling for pretargeted immunoPET of bispecific antibody using generator-produced 68Ga

Abstract

Bispecific antibody pretargeting is highly sensitive and specific for cancer detection by PET. In this study, the preparation of a high-specific-activity 68Ga-labeled hapten-peptide, IMP288, was evaluated. Methods: IMP288 (DOTA-D-Tyr-D-Lys(histamine- succinyl-glycine [HSG])-D-glu-D-Lys(HSG)-NH2) was added to buffered 68Ga and then heated in boiling water and purified on a reversed-phase cartridge. Tumor-bearing nude mice were used for biodistribution and tumor localization studies. Results: 68Ga-IMP288 was prepared at a starting specific activity up to 1.78 GBq/nmol, with final yields of 0.74 GBq/nmol (decay-corrected) and less than 1% unbound 68Ga. Purification was essential to remove unbound 68Ga and 68Ge breakthrough. Pretargeted animals showed a high 68Ga-IMP288 uptake (27.5±5.8 percentage injected dose per gram), with ratios of 13.6±4.8, 66.8±14.5, and 325.9±61.9 for the kidneys, liver, and blood, respectively, at 1.5 h after peptide injection. Conclusion: High-specific- activity labeling of DOTA-haptenpeptide was obtained from the 68Ga/68Ge generator for approximately 1 y, yielding products suitable for immunoPET. Copyright © 2011 the American Physiological Society.