The emerging value of 64Cu for molecular imaging and therapy

Along with other novel metallic radionuclides, copper-64 (64Cu) is currently being investigated as an alternative option to the gallium-68 (68Ga) and lutetium-177 (177Lu) radiopharmaceuticals widely used for targeting somatostatin receptors, expressed by neuroendocrine tumors (NETs), and recently prostate specific membrane antigen (PSMA), expressed by prostate cancer cells. This interest is mostly driven by the peculiar nuclear properties of 64Cu that make it an almost ideal example of theranostic radionuclide. In fact, 64Cu emits both low-energy positrons, β- particles and a swarm of Auger electrons. This combination of different emissions may allow to collect high-resolution PET images, but also to use the same radiopharmaceutical for eliciting a therapeutic effect. Another unique behavior of 64Cu originates from the fundamental biological role played in organisms by the ionic forms of the copper element, which is naturally involved in a multitude of cellular processes including cell replication. These intrinsic biological characteristics has led to the discovery that 64Cu, under its simplest dicationic form Cu2+, is able to specifically target a variety of cancerous cells and to detect the onset of a metastatic process in its initial stage. This short review reports an outline of the status of 64Cu radiopharmaceuticals and of the most relevant results that are constantly disclosed by preclinical and investigational clinical studies.