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

Karacay, Habibe; Sharkey, Robert M; McBride, William J; Rossi, Edmund A; Chang, Chien-Hsing; Goldenberg, David M · J Nucl Med · 2011

basic_science · Level V

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Abstract

Bispecific antibody pretargeting is highly sensitive and specific for cancer detection by PET. In this study, the preparation of a high-specific-activity (68)Ga-labeled hapten-peptide, IMP288, was evaluated. IMP288 (DOTA-D-Tyr-D-Lys(histamine-succinyl-glycine [HSG])-D-glu-D-Lys(HSG)-NH(2)) was added to buffered (68)Ga 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. (68)Ga-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 (68)Ga. Purification was essential to remove unbound (68)Ga and (68)Ge breakthrough. Pretargeted animals showed a high (68)Ga-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. High-specific-activity labeling of DOTA-hapten-peptide was obtained from the (68)Ga/(68)Ge generator for approximately 1 y, yielding products suitable for immunoPET.

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