Microwave-Supported Preparation of 68Ga Bioconjugates with High Specific Radioactivity

Abstract

The generator-produced positron-emitting ⁶⁸Ga (T_1/2 = 68 min) is of potential interest for clinical PET. ⁶⁸Ga as a metallic cation is suitable for complexation reactions with chelators, naked or conjugated, with peptides or other macromolecules. Large ⁶⁸Ga 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 ⁶⁸Ga concentration, second to purify it from competing impurities, and third to obtain a fast and quantitative ⁶⁸Ga-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 μL ⁶⁸Ga preparation (volume reduction by a factor 30) that is suitable for direct and quantitative labeling of peptide conjugates. DOTATOC (DOTA-d-Phe¹-Tyr³-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 ⁶⁸Ga preparations. In combination with microwave heating, peptide conjugates of 0.5−1 nmol quantities could be labeled within 10 min with the full ⁶⁸Ga activity of a generator. Further purification of the ⁶⁸Ga-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 ∼100 compared to the previously applied techniques using the original generator eluate. The commercial ⁶⁸Ge/⁶⁸Ga 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 ⁶⁸Ga-tracer production. The first automated prototype using this technology is being tested.