title: Peptide targeted copper-64 radiopharmaceuticals.
abstract: 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 ⁶⁴Cu-labelled 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.
authors.affiliation: School of Chemistry, University of Melbourne, Parkville, Melbourne, Victoria 3010, Australia.
authors.forename: Michelle T
authors.initials: MT
authors.lastname: Ma
authors.forename: Paul S
authors.initials: PS
authors.lastname: Donnelly
mesh_terms: D000818:Animals; D003301:Copper Radioisotopes / Q000737:chemistry; D006801:Humans; D009369:Neoplasms / Q000000981:diagnostic imaging*; D010455:Peptides / Q000737:chemistry; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: D003301:Copper Radioisotopes; D010455:Peptides; D019275:Radiopharmaceuticals