Characterization of SnO2-based 68Ge/68Ga generators and 68Ga-DOTATATE preparations: radionuclide purity, radiochemical yield and long-term constancy

Abstract

Background: With the increasing utilization of 68Ge-68Ga radionuclide generators, 68Ga labelled peptides like DOTATATE are receiving more attention in nuclear medicine. On the one hand, the long half-life of the parent nuclide 68Ge is an enormous advantage for routine applications, but the question of the long-term stability of the 68Ge breakthrough arises, which up to now has scarcely been investigated. Method: A sum of 123 eluates from four different 68Ge-68Ga generators (iThemba Labs, Faure, South Africa) and 115 samples of the prepared radiopharmaceutical 68Ga-DOTATATE were measured first with a dose calibrator and again after decay of the eluted 68Ga via gamma-ray spectrometry. A complete decay curve was recorded for one sample eluate. A further three eluates were eluted in ten fractions of 0.5 ml in order to obtain detailed information concerning the distribution of the two nuclides within the eluates. The influences of factors such as the amount of DOTATATE, addition of Fe3+ salts and replacement of HEPES buffer with sodium acetate on the radiochemical synthesis were also tested. Results: The content of long-lived 68Ge breakthrough increases over the entire period of use to more than 100 ppm. The labelling process with the chelator DOTA removes 68Ge efficiently. The maximum activity found in the residues of the radiopharmaceuticals investigated in this study was below 10 Bq in nearly all cases. In many cases (12% of the labelled substance), the long-lived parent nuclide could not be identified at all. The labelling process is still viable for reduced amounts of the chelator and with acetate buffer. Conclusion: Effective doses received by the patient from 68Ge in the injected radiopharmaceutical 68Ga-DOTATATE are lower than 0.1 μSv and are therefore practically negligible, especially when compared with the contribution of the PET radiopharmaceutical itself. Gamma-ray spectrometry as recommended by the European Pharmacopeia is suitable for quantification of radionuclidic impurities.