Receptor Targeting for Tumor Localisation and Therapy with Radiopeptides

Abstract

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 111In, 86Y, 90Y, 67Ga, 68Ga and 64Cu or for 99mTc and 188Re. and were labelled with the halogens 123I and 18F. Radiolabeled analogs of &alpha-melanocyte-stimulating hormone (&alpha-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-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA): [D-Phe1]-octreotide (DOTAOC), [D-Phe1, Tyr3]-octreotide (DOTATOC), vapreotide (DOTAVAP) and lanreotide (DOTALAN). DOTA is almost a universal chelator capable of strongly encapsulating hard metals such as 111In and 67Ga for Single Photon Emission Tomography (SPET), 68Ga, 86Y and 64Cu for Positron Emission Tomography (PET) as well as 90Y 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.

Comparison of two purified toxic fractions from Mesobuthus eupeus scorpion venom

“…The halflife is short enough to enable the administration of reasonably high doses which, in turn, allow good quality images. Moreover, 99mTc is available from 99Mo/99mTc generators in high quality and at low cost (21).…”

Radiolabeled somatostatin receptor antagonists are preferable to agonists forin vivopeptide receptor targeting of tumors

“…The best clinically established system for in vivo tumor targeting with radiolabeled peptides (1) is based on the somatostatin receptor, and a particularly large number of excellent radioligands have been developed for that purpose, all derived from somatostatin agonists (16). The first part of the present study deals with somatostatin receptor subtype 3 (sst 3 ).…”

“…For comparison, the accumulation of radioactivity in the sst 3 -expressing tumors by using the agonist 111 In-DOTA-NOC is considerably less than by using the antagonist 111 In-DOTA-sst 3 -ODN-8 and amounts to Ϸ7%IA͞g at 4 h and decreases at 24 h ( Table 3). The calculated tumor͞tissue ratios, representing important parameters to evaluate the quality of a targeting agent (16), are considerably higher with 111 In-DOTA-sst 3 -ODN-8 than with 111 In-DOTA-NOC, especially for the tumor͞blood and tumor͞muscle ratios at 4 and 24 h. Established sst 2 -expressing organs, such as the stomach, adrenals, or pancreas, show a blockable accumulation of 111 In-DOTA-NOC (Table 3), whereas they show no significant accumulation of 111 In-DOTA-sst 3 -ODN-8 ( Table 2). As a negative control, labeling of the sst 3 -expressing tumor with a specific sst 2 agonist radioligand, 111 In-DTPA-TATE (22), is found to be negligible ( (Table 1).…”

Lanthanide(III) Complexes of DOTA–Glycoconjugates: A Potential New Class of Lectin‐Mediated Medical Imaging Agents

“…[1][2][3][4] However, the central question in the development of new radiopharmaceutical agents is how to deliver them specifically to the cellular targets (receptors). Many strategies have been attempted and some are currently in clinical use.…”