New ⁶⁴Cu PET imaging agents for personalised medicine and drug development using the hexa-aza cage, SarAr

The success of positron emission tomography (PET) in personalised medicine and drug development requires radioisotopes that provide high quality images and flexible chemistry for a broad application. ⁶⁴Cu is arguably one of the most suitable PET isotopes for imaging with the evolving target agents, but there are not many appropriate chelating agents for ⁶⁴Cu and this has limited its wider application. The bi-functional chelator, SarAr is known to bind ⁶⁴Cu²⁺ quantitatively (i.e. one metal per ligand present) and rapidly (<2 min) at 10^-6 M over a range of pH (4-9). In this paper the conjugation of SarAr to the whole and fragmented antibody is described. Conjugation of the SarAr to the protein does not impair its coordination of the ⁶⁴Cu. It complexes the ⁶⁴Cu ²⁺ rapidly, quantitatively and essentially irreversibly at pH 5. Animal studies show that the ⁶⁴Cu-SarAr-immunoconjugates maintain their specificity for the target and are stable in vivo. Also, SarAr is a platform technology, is easy to use in a kit formulation and is readily adaptable for the wider application in ⁶⁴Cu PET imaging.