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

Abstract

BACKGROUND:

Previous studies have shown that the compact structure of a rhenium-cyclized alpha--melanocyte-stimulating hormone peptide analog, [Cys3410,D-Phe7]alpha-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-CCMSH 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-alpha-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 alpha-MSH analogs used in this study. Moreover, (111)In-DOTA-Re-CCMSH displayed 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.

• Authors: JianQing Chen, Zhen Cheng, Yubin Miao, Silvia S Jurisson, Thomas P Quinn
• Journal: Cancer (Cancer) Vol. 94 Issue 4 Suppl Pg. 1196-201 (Feb 15 2002) ISSN: 0008-543X [Print] United States
• PMID: 11877745 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
• Copyright: Copyright 2002 American Cancer Society.

Chemical References

• Antineoplastic Agents
• Peptide Fragments
• Indium
• alpha-MSH
• Technetium

Topics

• Animals
• Antineoplastic Agents (chemistry, pharmacokinetics)
• Disease Models, Animal
• Drug Delivery Systems (methods)
• Female
• Indium (chemistry, pharmacokinetics)
• Melanoma (metabolism)
• Mice
• Mice, Inbred C57BL
• Peptide Fragments (chemistry, pharmacokinetics)
• Radiotherapy
• Technetium (chemistry, pharmacokinetics)
• Tissue Distribution
• alpha-MSH (chemistry, pharmacokinetics)