Peptide Targeted Copper-64 Radiopharmaceuticals

Peptide targeted 64Cu-labelled diagnostic agents for positron emission tomography are viable candidates for molecular imaging of cancer. In a clinical setting, optimal image quality relies on selective tumor uptake of the 64Culabelled radiotracer. The three components of the radiotracer construct - the chelate group, linker and targeting peptide - all influence the biodistribution of the 64Cu-labelled radiotracer in vivo. Low or moderate Cu complex stability in vivo results in transmetallation of 64Cu to endogenous proteins, giving rise to high background activity. The length and the nature of the linker group affect the affinity of the 64Cu-labelled radiotracer for the target receptor. Variations in the peptide sequence can impact on the metabolic stability and therefore the bioavailability and tumor retention of the 64Cu-labelled radiotracer in vivo. Lastly, the hydrophilicity of the construct can influence radiotracer metabolism and clearance pathways. Recent advances in the field of peptide targeted 64Cu-labelled radiopharmaceuticals involve GRPR-targeted and αvβ3 integrin receptor-targeted constructs. These constructs are based on the bombesin peptide sequence and the RGD recognition motif respectively. These examples are reviewed as case studies in the optimisation of 64Cu radiotracer design.