Optimization of automated radiosynthesis of gallium-68-labeled PSMA11 with two 68Ge/68Ga generators: fractional elution or prepurification?

Abstract

Background Prostate cancer is one of the most common forms of cancer in men. An imaging technique for its diagnosis is [68Ga]-prostate specific membrane antigen (68Ga-PSMA-11) positron emission tomography (PET). Gallium 68 (68Ga) is typically obtained using a germanium 68/gallium 68 (68Ge/68Ga) generator, allowing for the diagnostic drug to be made readily available in the nuclear medicine department through elution. To meet the increasing demand for 68Ga labeled peptides and to reduce the cost of radiosynthesis, it is therefore necessary to optimize the elution process of 68Ge/68Ga generators. This study aims to identify the most effective approach for optimizing radiosynthesis using double elution in parallel of two 68Ge/68Ga generators. Two methods have been tested: one using prepurification, and the other using fractionated elution. Results Five synthesis sequences were conducted using each method. The mean labeling yields for double elution with prepurification were 45.8 ± 29.4 (mean ± standard deviation) and none met the required criteria. The mean labeling yields for the fractionated double elution were 97.5 ± 1.9 (mean ± standard deviation) meeting the criteria, significantly superior to the prepurification method (p=0.012), and similar to those of simple elution. There was no significant difference in the elution yields of both methods. Conclusions This study showed that fractionated double elution from 68Ge/68Ga generators produced a significantly higher labeling yield than double elution with prepurification, resulting in a larger activity recovered by radiosynthesis, and thereby allowing for more diagnostic tests to be performed. Additionally, this method does not add complexity or synthesis time compared to simple elution labeling, and could also be applied to other 68Ga labeled peptides.