α–melanocyte-stimulating hormone peptide analogs labeled with technetium-99m and indium-111 for malignant melanoma targeting

✍ Scribed by JianQing Chen; Zhen Cheng; Yubin Miao; Silvia S. Jurisson; Thomas P. Quinn

• Publisher: John Wiley and Sons
• Year: 2002
• Tongue: English
• Weight: 93 KB
• Volume: 94
• Category: Article
• ISSN: 0008-543X
• DOI: 10.1002/cncr.10284

✦ Synopsis

BACKGROUND.

Previous studies have shown that the compact structure of a rhenium-cyclized ␣-melanocyte-stimulating hormone peptide analog, [Cys 3,4,10 ,D- Phe 7 ]␣-MSH 3-13 , 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.

METHODS. Biodistribution properties

of indium-111 ( 111 In)-labeled DOTA-Re-CC- MSH were compared with the non-DOTA-containing technetium-99m ( 99m Tc)-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 111 In-DOTA-Re-CCMSH were also compared with other related cyclic and linear 111 In-labeled DOTA-␣-MSH complexes.

RESULTS.

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 111 In-DOTA-Re-CCMSH was significantly higher than the other 111 In-DOTA-coupled cyclic or linear ␣-MSH analogs used in this study. Moreover, 111 In-DOTA-Re-CCMSH dis- played lower radioactivity accumulation in normal tissues of interest than its non-Re-cyclized counterpart, 111 In-DOTA-CCMSH; the disulfide bond-cyclized 111 In-DOTA-CMSH; or the linear 111 In-DOTA-NDP.

CONCLUSIONS.

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.