Candidates for Peptide Receptor Radiotherapy Today and in the Future

Abstract

Regulatory peptide receptors are overexpressed in numerous human cancers. These receptors have been used as molecular targets by which radiolabeled peptides can localize cancers in vivo and, more recently, to treat cancers with peptide receptor radiation therapy (PRRT). This review describes the candidate tumors eligible for such radiotherapy on the basis of their peptide receptor content and discusses factors in PRRT eligibility. At the present time, PRRT is performed primarily with somatostatin receptor- and cholecystokinin-2 (CCK2)-receptor-expressing neuroendocrine tumors with radiolabeled octreotide analogs or with radiolabeled CCK2-selective analogs. In the future, PRRT may be extended to many other tumor types, including breast, prostate, gut, pancreas, and brain tumors, that have recently been shown to overexpress several other peptide receptors, such as gastrin-releasing peptide-, neurotensin-, substance P-, glucagon-like peptide 1-, neuropeptide Y-, or corticotropin-releasing factor-receptors. A wide range of radiolabeled peptides is being developed for clinical use. Improved somatostatin or CCK₂ analogs as well as newly designed bombesin, neurotensin, substance P, neuropeptide Y, and glucagon-like peptide-1 analogs offer promise for future PRRT.