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

Abstract: Objectives: PET scintigraphy with 68Ga-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 68Ge/68Ga 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 0.4–1GBq 68Ga in the eluate) and several concentration techniques of the eluate (HCl) were evaluated. The elution profiles of SnO2-based 68Ge/68Ga generators were monitored, while [HCl] of the eluens was varied from 0.3–1.0M. Metal ions and sterility of the eluate were determined by ICP. Fractionated elution and concentration of the 68Ga eluate were performed using anion and cation exchange. Concentrated 68Ga eluate, using all three concentration techniques, was used for labelling of DOTA-TATE. 68Ga-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 68Ga activity varies when the concentration of the eluens, HCl, was varied, while 68Ge activity remains virtually constant. SnO2-based 68Ge/68Ga generator elutes at 0.6M HCl >100% of the 68Ga activity at calibration time and ±75% after 300 days. Eluate at discharge was sterile and Endotoxins were <0.5EU/mL, RNP was always <0.01%. Metal ions in the eluate were <10ppm (in total). Highest desorption for anion purification was obtained with the 30mg 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 68Ga desorption of 68±8%. With all 68Ge/68Ga generators and for all 3 purification methods a SA up to 50MBq/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 68Ga with 1M 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 68Ga-DOTA-TATE of SPE columns varied, highest desorption was obtained with Baker C18 100mg (84%). Purification of 68Ga-DOTA-TATE by SPE resulted in an RNP of <10−4%. Conclusions: Eluate of SnO2-based 68Ge/68Ga generator, either by fractionated elution as by ion exchange can be used for labelling DOTA-peptides with 68Ga at a SA of 50MBq/nmol at >95% incorporation and a RCP of ±90%. SPE columns are very effective to increase RNP. [Copyright &y& Elsevier]