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

Abstract

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

Comparative Biodistribution and Radiation Dosimetry of 68Ga-DOTATOC and 68Ga-DOTATATE in Patients with Neuroendocrine Tumors

“…68 Ga (half-life, 68 min; b 1 decay, 89%; electron capture, 11%) was eluted with 0.6 M HCl from a 68 Ge/ 68 Ga-generator (1,850 MBq; IDB Holland BV), where 68 Ge (half-life, 270.8 d) was attached to a column of an inorganic matrix based on tin dioxide. Production and quality control of the tracers were compliant with good manufacturing practices and were accomplished within 1 h. The fractionation method was used for the labeling (8). The first 1.0-mL fraction was sent to the waste, and the next 1.0 mL, containing over 65% of the total radioactivity, was collected and buffered with 200 mL of acetate buffer and 60 mL of sodium hydroxide to provide a pH of 4.6 6 0.4.…”

Biodistribution and Radiation Dosimetry of the Anti-HER2 Affibody Molecule 68Ga-ABY-025 in Breast Cancer Patients

“…68 Ga-ABY-025 was produced in compliance with good manufacturing practices (18) using a fractionation method (19). 68 …”

Quantitative and Qualitative Intrapatient Comparison of 68Ga-DOTATOC and 68Ga-DOTATATE: Net Uptake Rate for Accurate Quantification

“…Good manufacturing practice-compliant production (21) of the tracers was accomplished within 1 h using a fractionation method (22) with subsequent product purification (23).…”