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.
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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.)
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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)
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