Receptor targeting for tumor localisation and therapy with radiopeptides

Receptor targeting with radiolabeled peptides has become very important in nuclear oncology in the past few years. The most frequently used peptides i n the clinic are analogs of somatostatin (SRIF), e.g. OctreoScan, which con tain chelators for the radioisotopes (111)ln, Y-86, Y-90, Ga-67, Ga-68 and Cu-64 Or for (TC)-T-99m and Re-188. and were labelled with the halogens I-1 23 and F-18. Radiolabeled analogs of a-melanocyte-stimulating hormone (a-MS H), neurotensin, vasoactive intestinal peptide (VIP), bombesin (BN), substa nce P (SP) and gastrin/cholecystokinin (CCK) are also being developed, eval uated in vitro and in vivo and tested for clinical application. This review focuses on the expression in tumors and the regulation of receptors for th ese neuropeptides as well as the development of novel chelator-peptide conj ugates suitable for in vivo scintigraphy or internal radiotherapy. The stat e of the art of radiopeptide pharmaceuticals is illustrated with four SRIF analogs, modified with the macrocyclic chelator 1, 4, 7, 10-telraazacyclodo decane-1, 4, 7, 10-tetraacetic acid (DOTA): [D-Phe(1)]-octreotide (DOTAOC), [D-Phe(1), Tyr(3)]-octreotide (DOTATOC), vapreotide (DOTAVAP) and lanreoti de (DOTALAN). DOTA is almost a universal chelator capable of strongly encap sulating hard metals such as (111)ln and Ga-67 for Single Photon Emission T omography (SPET), Ga-68, Y-86 and Cu-64 for Positron Emission Tomography (P ET) as well as Y-90 for receptor-mediated radionuclide therapy and radiolan thanides which exhibit different interesting decay schemes. From biodistrib ution studies in experimental animals and from clinical data it is conclude d that DOTATOC is currently the most suitable SRIF radiopeptide with the be st potential in the clinic.