• peptide;
  • α–melanocyte-stimulating hormone;
  • radiolabeling;
  • biodistribution;
  • melanoma targeting



Previous studies have shown that the compact structure of a rhenium-cyclized α–melanocyte-stimulating hormone peptide analog, [Cys3, 4, 10,D-Phe7]α-MSH3–13, or Re-CCMSH, significantly enhanced its in vivo tumor uptake and retention. In this study, the metal chelate 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was coupled to the N-terminus of Re-CCMSH in order to develop a melanoma-targeting peptide that could be labeled with a wider variety of imaging and therapeutic radionuclides.


Biodistribution properties of indium-111 (111In)–labeled DOTA-Re-CCMSH were compared with the non-DOTA-containing technetium-99m (99mTc)–CCMSH in murine melanoma–bearing C57 mice to determine the effects of DOTA on tumor uptake and whole-body clearance. The tumor targeting capacity and clearance kinetics of 111In-DOTA-Re-CCMSH were also compared with other related cyclic and linear 111In-labeled DOTA-α-MSH complexes.


The in vivo distribution data showed that the conjugation of DOTA to Re-CCMSH did not reduce its initial tumor uptake kinetics but did enhance its tumor retention and renal clearance properties. The tumor uptake of 111In-DOTA-Re-CCMSH was significantly higher than the other 111In-DOTA–coupled cyclic or linear α-MSH analogs used in this study. Moreover, 111In-DOTA-Re-CCMSH displayed lower radioactivity accumulation in normal tissues of interest than its non-Re-cyclized counterpart, 111In-DOTA-CCMSH; the disulfide bond–cyclized 111In-DOTA-CMSH; or the linear 111In-DOTA-NDP.


Peptide cyclization via rhenium coordination significantly enhanced the tumor targeting and renal clearance properties of DOTA-Re-CCMSH, making it an excellent candidate for melanoma radiodetection and radiotherapy. Cancer 2002;94:1196–1201. © 2002 American Cancer Society.

DOI 10.1002/cncr.10284