Accelerator production, radiochemical separation and nanoradiopharmaceutical formulation using ⁶⁹Ge: A next generation PET probe

Positron emission tomography (PET) has revolutionized the field of molecular imaging of cancer. The driving forces in the latest resurgence of PET are the advances in nano-oncology and availability of newer radioisotopes with attractive nuclear decay characteristics. Germanium-69 (Ge-69; T-1/2 = 39 h, 21 % beta(+), E-max = 1205 keV) is one such radioisotope whose potential is yet to be fully explored for PET imaging. The adequately long half-life of Ge-69, makes it an ideal choice for PET imaging using radiolabeled nanoformulations, which are expected to circulate for a relatively longer time in the biological system. In this study, we report the production of Ge-69 via Ga-69 (p, n) Ge-69 reaction using natural Ga2O3 target. A facile radiochemical separation method based on selective precipitation of Ga at pH similar to 7 was developed for isolating no-carrier-added (NCA) Ge-69 from the irradiated target in a form suitable for in vivo animal studies. A chelator-free approach was optimized for radiolabeling superparamagnetic arginine grafted iron oxide nanoparticles (AMNPs) with Ge-69 for potential use in dual modality PET/magnetic resonance imaging (MRI) and magnetic hyperthermia therapy of cancer. The radiolabeling yield of Ge-69-AMNPs was >95 % and the radiolabeled nanoformulation was stable even after 72 h. As a proof of concept, the suitability of the radiolabeled nanoformulation for in vivo PET imaging was demonstrated in Wistar rats. Overall, this strategy of production, radiochemical separation and radiopharmaceutical formulation might aid towards development of potent agents for cancer theranostics.