Kit-based preparation of [68Ga]Ga-P16-093 (PSMA-093) using different commercial 68Ge/68Ga generators

Prostate-specific membrane antigen (PSMA) is an important biomarker for molecular imaging and a target for radionuclide therapy of prostate cancer. Recently, U.S. Food and Drug Administration (FDA) has approved [68Ga]Ga-PSMA-11 as a PSMA-targeted positron emission tomography (PET) imaging agent for the diagnosis of prostate cancer. As an alternative PSMA imaging agent, [68Ga]Ga-P16-093 ([68Ga]Ga-PSMA-093) showed excellent blood clearance and rapid tumor uptake, desirable in vivo properties for avidly detecting primary tumor and metastatic lesions in patients. To improve the availability and test the robustness of radiolabeling reaction, eluents of 68Ga/HCl from different sources of generators were evaluated.Commercially available 68Ge/68Ga generators from Eckert & Ziegler, ITG and iThemba were eluted with varying molarities of hydrochloric acid (0.05-0.6 M, as recommended by each company) and reacted with P16-093 kits. Radiolabeling yields, in vitro stabilities, in vitro cell uptakes and drug release criteria of different preparations were investigated. PET/computed tomography (CT) imaging of prostate cancer patients with [68Ga]Ga-P16-093 produced by using different sources of 68Ga were performed.Optimized P16-093 kit containing 15 μg of P16-093 (precursor) and 68 mg of sodium acetate trihydrate (buffer), a formulation previously tested in humans, was successfully labeled with eluents from Eckert & Ziegler, ITG and iThemba's generators. In vitro cell uptake studies showed that [68Ga]Ga-P16-093, formulated with ITG and iThemba's generators, exhibited equivalent PSMA-specific uptakes. Clinical studies in prostate cancer patients exhibited exceedingly comparable maximum standardized uptake value (SUVmax) for each lesion regardless of source of the generator used in preparation.Using different vendors' generator and lyophilized P16-093 kits, [68Ga]Ga-P16-093 could be conveniently and reliably prepared by a simple one-step reaction with excellent yields. Clinically useful doses of [68Ga]Ga-P16-093 imaging tracer could be made available using different 68Ge/68Ga generators.