Synthesis of a novel bifunctional chelator AmBaSar based on sarcophagine for peptide conjugation and 64Cu radiolabelling

Copper-64 shows promise as both a suitable PET imaging and therapeutic radionuclide due to its nuclear characteristics. Stable attachment of radioactive Cu-64(2+) to targeted imaging probes requires the use of a bifunctional chelator. Sarcophagine (Sar) ligands coordinate the metal ion Cu-64(2+) within the multiple macrocyclic rings comprising the cage structure, yielding extraordinarily stable complexes that are inert to dissociation of the metal ion in vivo. Several Cu-64 labelled RGD derivatives have been applied in imaging of the alpha(v)beta(3) integrin receptor expression during tumour angiogenesis. In order to design and develop novel molecular imaging probes containing RGD and Sar ligands, we designed a novel versatile Sar cage-like bifunctional chelator named AmBaSar, synthesized using a conventional synthetic strategy. Conjugation with the cyclic peptide RGD, and subsequent labelling with Cu-64, provided a new PET probe Cu-64-AmBaSar-RGD for imaging the alpha(v)beta(3) integrin receptor.