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 in the clinic are analogs of somatostatin (SRIF), e.g. OctreoScan, which contain 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-123 and F-18. Radiolabeled analogs of a-melanocyte-stimulating hormone (a-MSH), neurotensin, vasoactive intestinal peptide (VIP), bombesin (BN), substance P (SP) and gastrin/cholecystokinin (CCK) are also being developed, evaluated in vitro and in vivo and tested for clinical application. This review focuses on the expression in tumors and the regulation of receptors for these neuropeptides as well as the development of novel chelator-peptide conjugates suitable for in vivo scintigraphy or internal radiotherapy. The state of the art of radiopeptide pharmaceuticals is illustrated with four SRIF analogs, modified with the macrocyclic chelator 1, 4, 7, 10-telraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA): [D-Phe(1)]-octreotide (DOTAOC), [D-Phe(1), Tyr(3)]-octreotide (DOTATOC), vapreotide (DOTAVAP) and lanreotide (DOTALAN). DOTA is almost a universal chelator capable of strongly encapsulating hard metals such as (111)ln and Ga-67 for Single Photon Emission Tomography (SPET), Ga-68, Y-86 and Cu-64 for Positron Emission Tomography (PET) as well as Y-90 for receptor-mediated radionuclide therapy and radiolanthanides which exhibit different interesting decay schemes. From biodistribution studies in experimental animals and from clinical data it is concluded that DOTATOC is currently the most suitable SRIF radiopeptide with the best potential in the clinic.