Characteristics of SnO2-based 68Ge/68Ga generator and aspects of radiolabelling DOTA-peptides

Objectives: PET scintigraphy with Ga-68-labelled analogs is of increasing interest in Nuclear Medicine and performed all over the world. Here we report the characteristics of the eluate of SnO2-based Ge-68/Ga-68 generators prepared by iThemba LABS (Somerset West, South Africa). Three purification and concentration techniques of the eluate for labelling DOTA-TATE and concordant SPE purifications were investigated. Methods: Characteristics of 4 SnO2-based generators (range 0.4-1 GBq Ga-68 in the eluate) and several concentration techniques of the eluate (HCl) were evaluated. The elution profiles of SnO2-based Ge-68/Ga-68 generators were monitored, while [HCl] of the eluens was varied from 0.3-1.0 M. Metal ions and sterility of the eluate were determined by ICP. Fractionated elution and concentration of the Ga-68 eluate were performed using anion and cation exchange. Concentrated Ga-68 eluate, using all three concentration techniques, was used for labelling of DOTA-TATE. Ga-68-DOTA-TATE-containing solution was purified and RNP increased by SPE, therefore also 11 commercially available SPE columns were investigated. Results: The amount of elutable Ga-68 activity varies when the concentration of the eluens, HCl, was varied, while Ge-68 activity remains virtually constant. SnO2-based Ge-68/Ga-68 generator elutes at 0.6 M HCl > 100% of the Ga-68 activity at calibration time and +/- 75% after 300 days. Eluate at discharge was sterile and Endotoxins were < 0.5 EU/mL, RNP was always < 0.01%. Metal ions in the eluate were < 10 ppm (in total). Highest desorption for anion purification was obtained with the 30 mg Oasis WAX column (> 80%). Highest desorption for cation purification was obtained using a solution containing 90% acetone at increasing molarity of HCl, resulted in a Ga-68 desorption of 68 +/- 8%. With all Ge-68/Ga-68 generators and for all 3 purification methods a SA up to 50 MBq/nmol with > 95% incorporation (ITLC) and RCP (radiochemical purity) by HPLC +/- 90% could be achieved. Purification and concentration of the eluate with anion exchange has the benefit of more elutable Ga-68 with 1 M HCl as eluens. The additional washing step of the anion column with NaCl and ethanol, resulted in a lower and less variable [H+] in the eluate, and, as a result the pH in the reaction vial is better controlled, more constant, and less addition of buffer is required and concordant smaller reaction volumes. Desorption of Ga-68-DOTA-TATE of SPE columns varied, highest desorption was obtained with Baker C-18 100 mg (84%). Purification of Ga-68-DOTA-TATE by SPE resulted in an RNP of < 10(-4)%. Conclusions: Eluate of SnO2-based Ge-68/Ga-68 generator, either by fractionated elution as by ion exchange can be used for labelling DOTA-peptides with Ga-68 at a SA of 50 MBq/nmol at > 95% incorporation and a RCP of +/- 90%. SPE columns are very effective to increase RNP. (C) 2010 Elsevier Ltd. All rights reserved.