Strategies for improving stability and pharmacokinetic characteristics of radiolabeled peptides for imaging and therapy

Tumor cells overexpress a variety of receptors that are emerging targets in cancer chemotherapy. Radiolabeled peptides with high affinity and selectivity for these overexpressed receptors have been designed for both imaging and therapy purposes. Such peptides display advantages such as high selectivity for tumor cells, rapid tumor tissue penetration, and rapid clearance from non-target tissues and the circulation. However, the very short in vivo half-life of radiolabeled peptides, arising from enzymatic degradation and/or efficient clearance by the kidney, limits their accumulation in tumors. This review presents various strategies that have been applied to extend the half-life extension and improve the pharmacokinetic characteristics of radiolabeled peptides. These include amino acid substitution, modification of the peptide termini, dimerization and multimerization of the peptide, cyclization, conjugation with polymers, sugars and albumin and use of peptidase inhibitors.