Site-specific π-clamp-mediated radiosynthesis of ⁶⁸Ga and ¹⁸F PET radiopharmaceuticals

The π-clamp-mediated conjugation method, which enables site-specific modification of cysteine residues, is a promising strategy for developing well-defined radiolabelled biomolecules for positron emission tomography (PET) imaging. We have applied this method to site-specifically attach the macrocyclic chelators "NODA" and "NODAGA" to the somatostatin receptor 2-targeted peptide, octreotate. The resulting novel NODA-octreotate and NODAGA-octreotate compounds can be radiolabelled with either [¹⁸F]AlF^- or [⁶⁸Ga]Ga³⁺ respectively. In vivo PET imaging shows that the [⁶⁸Ga]Ga³⁺-labelled derivative exhibits high stability and favourable pharmacokinetic properties.