Cancer Targeting Radiopeptidomimetics in Molecular Nuclear Medicine

Peptides are highly receptor-affine molecules exhibiting suitable pharmacokinetics. Additionally, low-cost production, simple protocols allowing easy modifications, and tolerance toward harsh reaction conditions make peptides ideal ligands for preparation of radiopharmaceuticals for cancer detection and treatment. However, natural peptides being substrates for enzymes are susceptible to proteolysis, which limits the in vivo lifetime and the target uptake. Therefore, the majority of peptides are not able to progress beyond preclinical research. Advancement of peptides for clinical analysis needs modification to instill improved features. Continuous increase and further expected rise in cancer cases in the next decade require development of more disease-directed and promising radiopharmaceuticals. Redesigned peptide, mimicking the original peptide with similar or improved affinity and high metabolic stability, shall have significant edge. This review outlines the design of peptidomimetics by incorporation of D-amino acids (inverso); reversal of D-amino acid sequence (retro-inverso), and reversal of L-amino acid sequence (retro). Clinically successful radiopeptidomimetics prepared using the three approaches have been elaborated to elucidate the important role of peptidomimetics in cancer management.