Microwave-supported preparation of 68Ga bioconjugates with high specific radioactivity

The generator-produced positron-emitting Ga-68 (T-1/2 = 68 min) is of potential interest for clinical PET. Ga-68 as a metallic cation is suitable for complexation reactions with chelators, naked or conjugated, with peptides or other macromolecules. Large Ga-68 generator eluate volumes, metal traces from the generator column material, or reaction reagents, however, disturb a fast, reliable, and quantitative labeling procedure. In this paper we describe a simple technique, based on anion exchange, aiming first, to increase the Ga-68 concentration, second to purify it from competing impurities, and third to obtain a fast and quantitative Ga-68-labeled peptide conjugate that can be applied in humans without further purification. Within 5 min one can obtain from the original 6 mL generator eluate a 200 muL Ga-68 preparation (volume reduction by a factor 30) that is suitable for direct and quantitative labeling of peptide conjugates. DOTATOC (DOTA-D-Phe(1)-Tyr(3)-octreotide, DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) was used as a test tracer for comparing the labeling properties of the different Ga-68 preparations. In combination with microwave heating, peptide conjugates of 0.5-1 nmol quantities could be labeled within 10 min with the full Ga-68 activity of a generator. Further purification of the Ga-68-labeled peptide conjugate was no longer required since the nuclide incorporation was quantitative. The specific radioactivity (with respect to the peptide) was improved by a factor similar to100 compared to the previously applied techniques using the original generator eluate. The commercial Ge-68/Ga-68 generator from Obninsk in combination with this system for purification and concentration with an integrated microwave-supported labeling technology resulted in a kitlike technology for Ga-68-tracer production. The first automated prototype using this technology is being tested.