Recent advances in copper radiopharmaceuticals

Copper has five radioisotopes (⁶⁰Cu, ⁶¹Cu, ⁶²Cu, ⁶⁴Cu, and ⁶⁷Cu) that can be used in copper radiopharmaceuticals. These radioisotopes decay by mixed emissions of β⁺, β^-, and γ with a wide range of half-lives from 9.74 min (⁶²Cu) to 2.58 d (⁶⁷Cu), which enable the design and synthesis of a variety of radiopharmaceuticals for different biomedical applications in diagnostic and therapeutic nuclear medicine. However, due to the availability and production cost, the research efforts in copper radiopharmaceuticals are mainly focused on the use of ⁶⁴Cu (t_1/2 = 12.7 h; 17.4% β⁺, 43% EC, 39% β^-), a radioisotope with low positron energy (E_β+max = 0.656 MeV) that is ideal for positron emission tomography (PET) imaging quantification and β^- emissions along with Auger electron for radiotherapy. Driven by the ever-increasing availability of preclinical and clinical PET scanners, a considerable interest has been seen in the development of novel copper radiopharmaceuticals in the past decade for a variety of diseases as represented by PET imaging of cancer. To avoid unnecessary literature redundancy, this review focuses on the unrepresented research aspects of copper chemistry (e.g. electrochemistry) and their uses in the evaluation of novel nuclear imaging probe design and recent advances in the field towards the practical use of copper radiopharmaceuticals.