Smoothened titania particles to improve radionuclide separation and their application to the development of a novel [68Ge]/[68Ga] generator

Abstract

Gallium-68 has a high potential for clinical positron emission tomography (PET) because of its ⁶⁸Ge/⁶⁸Ga generator based production. Unfortunately, during elution of the gallium-68, generators usually display a germanium-68 breakthrough which consequently limits their use in a clinical context. To be more precise, usually used crude anatase presents fragile edges which can split and be co-eluted from the generator during gallium-68 recovery, resulting in metal and germanium-68 contaminations. The addition of a sonication step during the production process of titania induces more resistant smoothened particles which were packed in a quartz glass column to give a novel ⁶⁸Ge/⁶⁸Ga generator. The performance of the system (elution profile, elution yield and germanium-68 breakthrough) was determined and followed-up over a period of nine months in terms of reliability and efficiency so as to produce high quality gallium-68 and to radiolabel DOTA-peptides. Elution of gallium-68 from the generator was achieved with a constant yield (≈67 ± 5%) and a ⁶⁸Ge/⁶⁸Ga ratio typically lower than 2.0 × 10⁻⁷ which is about 20 fold less than the values observed using crude titania. Moreover, fully automated processes that involved a fractionated elution or a cation exchange preconcentration of gallium-68 were realized. [⁶⁸Ga]-radiotracer production occurred in less than 20 min with a marked radiochemical purity (>97%) and yield (80–90%, decay-corrected). We have shown experimentally that smoothened anatase based systems generated high quality gallium-68 which was successfully used for the labeling of DOTA-peptides in considerable radiochemical yields and radioactive purity throughout its expected life.