Recent developments in the design of bifunctional chelators for metal-based radiopharmaceuticals used in Positron Emission Tomography

In recent years, Positron Emission Tomography (PET) has become a practical, high performance clinical imaging modality for visualization of biological process within the living system. For radiolabeling of targeting vectors, ideally determining the biological fate of the radiolabeled bioconjugate, non-traditional metal-based PET radioisotopes are of particular interest as they offer certain advantages over traditional PET radioisotopes such as longer half-lives that allow delayed imaging or availability by commercial generator systems apart from on-site cyclotron production. However, for the incorporation of the radiometal into the targeting vector, a bifunctional chelator is needed that tightly binds the radiometal at one terminus while the second terminus serves for the covalent conjugation to the biomolecule. Conjugation of a metal chelate functionality to a biovector, however, may impact the in vivo distribution of the biomolecule. This review summarizes the recent developments of bifunctional chelates for two important PET radiometals, copper-64 and gallium-68, and discusses their coordination chemistry in relation to in vivo stability and pharmacokinetics. (C) 2012 Elsevier B.V. All rights reserved.