Copper-64, as a radionuclide, can be simultaneously used for both imaging and potential therapy, because of its specific nuclear characteristics, such as the half-life (12.7 h) and decay properties (β⁺, 0.653 MeV, 17.8%; β^-, 0.579 MeV, 38.4%). In the past two decades, with the well-established copper coordination chemistry, more and more novel ligands for copper-64 have been designed and synthesized, like DOTA, TETA, NOTA, CB-TE2A, C3B-DO2A, etc. Nowadays, copper-64 is able to bind not only with biologically relevant small molecules, but also with some antibodies, proteins, and nanoparticles. From another point of view, the stability of the copper-64-labeled radiopharmaceuticals has been significantly improved in both vitro and vivo tests. Thus, the exploration of novel ligands and receptors with new labeling strategies has become a hot issue in the copper radiopharmaceutical chemistry. Up to now, many new copper-64-labeled radiopharmaceuticals have been synthesized, some of which exhibit excellent biodistributions, as ⁶⁴Cu-ATSM is an effective radiopharmaceutical in imaging of hypoxic tissues and ⁶⁴Cu-PTSM is a good blood flow tracer, etc. This paper will selectively review some new labeling methods for copper-64-labeled radiopharmaceuticals, and some potential applications of these coordination compounds in both imaging and therapy. The perspectives of this field is addressed as well. Contents 1 Introduction
2 The ligands for copper-64
2.1 Azamacrocyclic ligands
2.2 Cross-bridged ligands
2.3 KTS/PTSM/ATSM
3 Application
3.1 Radiopharmaceuticals for imaging
3.2 Radiotherapy
4 Conclusion and outlook