Bioconjugates of Chelators with Peptides and Proteins in Nuclear Medicine: Historical Importance, Current Innovations, and Future Challenges

Molecular radiopharmaceuticals based on bioconjugates of chelators with peptides and proteins have had significant clinical impact in the diagnosis and treatment of several types of cancers. In the 1990s, indium-111 and yttrium-90 labeled chelator-peptide/protein conjugates established the clinical utility of these radiopharmaceuticals for receptor-targeted γ-scintigraphy imaging and systemic radiotherapy. Second-generation bioconjugates based on peptides targeting the somatostatin II receptor and the prostate-specific membrane antigen are now widely used for management of neuroendocrine and prostate cancer, respectively. These bioconjugates are typically radiolabeled with gallium-68 for imaging of target receptor expression with positron emission tomography, and the β–-emitter, lutetium-177, for targeted radiotherapy. Innovations in radioisotope technology and biomolecular therapies are likely to drive the future clinical development of radiopharmaceuticals based on radiometals. New chelator–peptide and chelator–protein bioconjugates will underpin nuclear medicine advances in molecular imaging and radiotherapy.