Source:http://linkedlifedata.com/resource/pubmed/id/20728365
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
18
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pubmed:dateCreated |
2010-9-6
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pubmed:abstractText |
The purpose of this study was to reduce the non-specific renal uptake of Arg-Gly-Asp (RGD)-conjugated alpha-melanocyte stimulating hormone (alpha-MSH) hybrid peptide through structural modification or L-lysine co-injection. The RGD motif {cyclic(Arg-Gly-Asp-DTyr-Asp)} was coupled to [Cys(3,4,10), D-Phe7, Arg11] alpha-MSH3-13 {(Arg11)CCMSH} through the Arg linker (substituting the Lys linker) to generate a novel RGD-Arg-(Arg11)CCMSH hybrid peptide. The melanoma targeting and pharmacokinetic properties of 99mTc-RGD-Arg-(Arg11)CCMSH were determined in B16/F1 melanoma-bearing C57 mice. The effect of L-lysine co-injection on the renal uptake was determined through the co-injection of L-lysine with 99mTc-RGD-Arg-(Arg11)CCMSH or 99mTc-RGD-Lys-(Arg11)CCMSH. Replacement of the Lys linker with an Arg linker exhibited a profound effect in reducing the non-specific renal uptake of 99mTc-RGD-Arg-(Arg11)CCMSH, as well as increasing the tumor uptake of 99mTc-RGD-Arg-(Arg11)CCMSH compared to 99mTc-RGD-Lys-(Arg11)CCMSH. 99mTc-RGD-Arg-(Arg11)CCMSH exhibited high tumor uptake (21.41+/-3.74% ID/g at 2 h post-injection) and prolonged tumor retention (6.81+/-3.71% ID/g at 24 h post-injection) in B16/F1 melanoma-bearing mice. The renal uptake values of 99mTc-RGD-Arg-(Arg11)CCMSH were 40.14-64.08% of those of 99mTc-RGD-Lys-(Arg11)CCMSH (p<0.05) at 0.5, 2, 4 and 24 h post-injection. Co-injection of L-lysine was effective in decreasing the renal uptakes of 99mTc-RGD-Arg-(Arg11)CCMSH by 27.7% and 99mTc-RGD-Lys-(Arg11)CCMSH by 52.1% at 2 h post-injection. Substitution of the Lys linker with an Arg linker dramatically improved the melanoma uptake and reduced the renal uptake of 99mTc-RGD-Arg-(Arg11)CCMSH, warranting the further evaluation of 188Re-labeled RGD-Arg-(Arg11)CCMSH as a novel MC1 receptor-targeting therapeutic peptide for melanoma treatment in the future.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Arginine,
http://linkedlifedata.com/resource/pubmed/chemical/Lysine,
http://linkedlifedata.com/resource/pubmed/chemical/Melanocyte-Stimulating Hormones,
http://linkedlifedata.com/resource/pubmed/chemical/Oligopeptides,
http://linkedlifedata.com/resource/pubmed/chemical/Organoplatinum Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Technetium,
http://linkedlifedata.com/resource/pubmed/chemical/alpha-MSH,
http://linkedlifedata.com/resource/pubmed/chemical/arginyl-glycyl-aspartic acid
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1464-3391
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pubmed:author | |
pubmed:copyrightInfo |
Copyright (c) 2010 Elsevier Ltd. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:day |
15
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pubmed:volume |
18
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6695-700
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pubmed:dateRevised |
2011-9-26
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pubmed:meshHeading |
pubmed-meshheading:20728365-Amino Acid Sequence,
pubmed-meshheading:20728365-Animals,
pubmed-meshheading:20728365-Antineoplastic Agents,
pubmed-meshheading:20728365-Arginine,
pubmed-meshheading:20728365-Isotope Labeling,
pubmed-meshheading:20728365-Kidney,
pubmed-meshheading:20728365-Lysine,
pubmed-meshheading:20728365-Melanocyte-Stimulating Hormones,
pubmed-meshheading:20728365-Melanoma, Experimental,
pubmed-meshheading:20728365-Mice,
pubmed-meshheading:20728365-Mice, Inbred C57BL,
pubmed-meshheading:20728365-Oligopeptides,
pubmed-meshheading:20728365-Organoplatinum Compounds,
pubmed-meshheading:20728365-Technetium,
pubmed-meshheading:20728365-Whole Body Imaging,
pubmed-meshheading:20728365-alpha-MSH
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pubmed:year |
2010
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pubmed:articleTitle |
Replacement of the Lys linker with an Arg linker resulting in improved melanoma uptake and reduced renal uptake of Tc-99m-labeled Arg-Gly-Asp-conjugated alpha-melanocyte stimulating hormone hybrid peptide.
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pubmed:affiliation |
College of Pharmacy, University of New Mexico, Albuquerque, NM 87131, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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