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Evaluation of novel (99m)Tc(I)-labeled homobivalent α-melanocyte-stimulating hormone analogs for melanocortin-1 receptor targeting.
MedLine Citation:
PMID:  22286955     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Aiming to apply the multivalency concept to melanoma imaging, we have assessed the in vivo melanocortin type 1 receptor (MC1R)-targeting properties of (99m)Tc(I)-labeled homobivalent peptide conjugates which contain copies of the α-melanocyte-stimulating hormone (α-MSH) analog [Ac-Nle(4), Asp(5), D: -Phe(7), Lys(11)]α-MSH(4-11) separated by linkers of different length (L ( 2 ) nine atoms and L ( 3 ) 14 atoms). The MC1R-binding affinity of L ( 2 ) and L ( 3 ) is significantly higher than that of the monovalent conjugate L ( 1 ). Metallation of these conjugates yielded the complexes fac-[M(CO)(3)(k(3)-L)](+) (M is (99m)Tc/Re; 1/1a, L is L ( 1 ); 2/2a, L is L ( 2 ); 3/3a, L is L ( 3 )), with IC(50) values in the subnanomolar and nanomolar range. The MC1R-mediated internalization of 2 and 3 is higher than that of 1 in B16F1 melanoma cells. Biodistribution studies in melanoma-bearing mice have shown low nonspecific accumulation with a tumor uptake that correlates with IC(50) values. However, no correlation between tumor uptake and valency was found. Nevertheless, 2 displayed the highest tumor retention, and the best tumor to nontarget organ ratios.
Authors:
Maurício Morais; Paula D Raposinho; Maria Cristina Oliveira; João D G Correia; Isabel Santos
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-29
Journal Detail:
Title:  Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry     Volume:  -     ISSN:  1432-1327     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-1-30     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9616326     Medline TA:  J Biol Inorg Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Unidade de Ciências Químicas e Radiofarmacêuticas, ITN, Estrada Nacional 10, 2686-953, Sacavém, Portugal.
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