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α–melanocyte-stimulating hormone peptide analogs labeled with technetium-99m and indium-111 for malignant melanoma targeting
Article first published online: 12 FEB 2002
Copyright © 2002 American Cancer Society
Supplement: Eighth Conference on Radioimmunodetection and Radioimmunotherapy of Cancer
Volume 94, Issue Supplement 4, pages 1196–1201, 15 February 2002
How to Cite
Chen, J., Cheng, Z., Miao, Y., Jurisson, S. S. and Quinn, T. P. (2002), α–melanocyte-stimulating hormone peptide analogs labeled with technetium-99m and indium-111 for malignant melanoma targeting. Cancer, 94: 1196–1201. doi: 10.1002/cncr.10284
- Issue published online: 12 FEB 2002
- Article first published online: 12 FEB 2002
- Manuscript Accepted: 14 NOV 2001
- Manuscript Received: 31 OCT 2001
- Department of Energy. Grant Number: ER61661
- National Cancer Institute. Grant Number: CA85106
- α–melanocyte-stimulating hormone;
- 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.