68Ga-PET Radiopharmacy: A Generator-Based Alternative to 18F-Radiopharmacy

Abstract

Positron emission tomography (PET) is becoming a dominating method in the field of molecular imaging. Most commonly used radionuclides are accelerator produced ¹¹C and ¹⁸F. An alternative method to label biomolecules is the use of metallic positron emitters; among them ⁶⁸Ga is the most promising as it can be produced from a generator system consisting of an inorganic or organic matrix immobilizing the parent radionuclide ⁶⁸Ge. Germanium-68 has a long half-life of 271 days which allows the production of long-lived, potentially very cost-effective generator systems. A commercial generator from Obninsk, Russia, is available which uses TiO₂ as an inorganic matrix to immobilize ⁶⁸Ge in the oxidation state IV+. ⁶⁸Ge(IV) is chemically sufficiently different to allow efficient separation from ⁶⁸Ga(III). Ga³⁺ is redox-inert; its coordination chemistry is dominated by its hard acid character. A variety of mono- and bifunctional chelators were developed which allow immobilization of ⁶⁸Ga³⁺ and convenient coupling to biomolecules. Especially peptides targeting G-protein coupled receptors overexpressed on human tumour cells have been studied preclinically and in patient studies showing high and specific tumour uptake and specific localization. ⁶⁸Ga-radiopharmacy may indeed be an alternative to ¹⁸F-based radiopharmacy. Freeze-dried, kit-formulated precursors along with the generator may be provided, similar to the ⁹⁹Mo/^99m Tc-based radiopharmacy, still the mainstay of nuclear medicine.