Peptides for Nuclear Medicine Therapy: Chemical Properties and Production

Abstract

Tumor receptor targeting with radiolabeled peptides is gaining wide acceptance in nuclear medicine and nuclear oncology. This emerging strategy offer powerful treatments targeted against tumors that cannot be treated by other conventional methods. The overexpression of many peptide receptors in a variety of tumors, compared to their relatively low density in normal organs, represents the molecular basis for in vivo imaging and targeted radionuclide therapy with radiolabeled peptides. Radiopeptides that bind with high affinity and specificity to the receptors on tumor cells hold great potential for both diagnostic imaging and targeted radionuclide therapy. The advantage of solid-phase peptide synthesis, the availability of different bifunctional chelating agents, and bioconjugation techniques permit the facile preparation of a wide variety of peptide-based targeting molecules with diverse biological and tumor targeting properties. Some of these peptide families, including somatostatin, bombesin, vasoactive intestinal peptide, gastrin, neurotensin, exendin, and RGD have been explored during the past years and quite a number of radiolabeled peptides with clinical potential have been derived from them. On the other hand, a number of strategies and optimized protocols for efficient radiolabeling of peptides with clinically relevant radiometals, such as 111In, 86/90Y, 177Lu, 67/68Ga, and 64/67Cu have been developed. The choice of the labeling approach is driven by the nature and the chemical properties of the radiometals. Medically useful radiometals are of increased current interest because of the growing use of targeted radiotherapy of tumors. The most commonly used radionuclides for therapy are β-emitters, which have shorter penetration range than γ-emitters. Alpha or Auger emitters are also studied for higher therapeutic efficiency within shorter range. This chapter presents some characteristics of small peptides and their development as tumor targeting agents. Also different bifunctional chelators for peptide labeling, properties of therapeutic radionuclides and their applications in treatment of cancer are briefly discussed.