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 ⁶⁴Cu²⁺ to targeted imaging probes requires the use of a bifunctional chelator. Sarcophagine (Sar) ligands coordinate the metal ion ⁶⁴Cu²⁺ 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 ⁶⁴Cu labelled RGD derivatives have been applied in imaging of the α_νβ₃ 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 ⁶⁴Cu, provided a new PET probe ⁶⁴Cu- AmBaSar-RGD for imaging the α_νβ₃ integrin receptor.