Document Detail

Design and biological evaluation of ⁹⁹mTc-N₂S₂-Tat(49-57)-c(RGDyK): a hybrid radiopharmaceutical for tumors expressing α(v)β(3) integrins.
MedLine Citation:
PMID:  23618768     Owner:  NLM     Status:  MEDLINE    
METHODS: The c(RGDyK) peptide was conjugated to a maleimidopropionyl (MP) moiety through Lys, and the MP group was used as the branch position to form a thioether with the Cys(12) side chain of the Tat(49-57)-spacer-N₂S₂ peptide. (99m)Tc-Tat-RGD was prepared, and stability studies were carried out by size exclusion HPLC analyses in human serum. The in vitro affinity for α(v)β(3) integrin was determined by a competitive binding assay. In vitro internalization was determined using glioblastoma C6 cells. Biodistribution studies were accomplished in athymic mice with C6 induced tumors that had blocked and unblocked receptors. Images were obtained using a micro-SPECT/CT.
RESULTS: (99m)Tc-Tat-RGD was obtained with a radiochemical purity higher than 95%, as determined by radio-HPLC and ITLC-SG analyses. Protein binding was 15.7% for (99m)Tc-Tat-RGD and 5.6% for (99m)Tc-RGD. The IC50 values were 6.7 nM ((99m)Tc-Tat-RGD) and 4.6 nM ((99m)Tc-RGD). Internalization in C6 cells was higher in (99m)Tc-Tat-RGD (37.5%) than in (99m)Tc-RGD (10%). Biodistribution studies and in vivo micro-SPECT/CT images in mice showed higher tumor uptake for (99m)Tc-Tat-RGD (6.98% ± 1.34% ID/g at 3h) than that of (99m)Tc-RGD (3.72%±0.52% ID/g at 3h) with specific recognition for α(v)β(3) integrins.
CONCLUSIONS: Because of the significant cell internalization (Auger and internal conversion electrons) and specific recognition for α(v)β(3) integrins, the hybrid (99m)Tc-N₂S₂-Tat(49-57)-c(RGDyK) radiopharmaceutical is potentially useful for the imaging and possible therapy of tumors expressing α(v)β(3) integrins.
Blanca E Ocampo-García; Clara L Santos-Cuevas; Luis M De León-Rodríguez; Rocío García-Becerra; David Ordaz-Rosado; Myrna A Luna-Guitiérrez; Nallely P Jiménez-Mancilla; Mario E Romero-Piña; Guillermina Ferro-Flores
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Nuclear medicine and biology     Volume:  40     ISSN:  1872-9614     ISO Abbreviation:  Nucl. Med. Biol.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-04-26     Completed Date:  2013-11-26     Revised Date:  2014-07-31    
Medline Journal Info:
Nlm Unique ID:  9304420     Medline TA:  Nucl Med Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  481-7     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 Elsevier Inc. All rights reserved.
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MeSH Terms
Biological Transport
Cell Line, Tumor
Drug Design*
Gene Expression Regulation, Neoplastic*
Glioma / metabolism*,  pathology,  radionuclide imaging
Integrin alphaVbeta3 / metabolism*
Multimodal Imaging
Oligopeptides / chemistry*
Organotechnetium Compounds / chemistry,  diagnostic use*,  metabolism,  pharmacokinetics
Peptide Fragments / chemistry*
Radiopharmaceuticals / chemistry,  diagnostic use,  metabolism,  pharmacokinetics
tat Gene Products, Human Immunodeficiency Virus / chemistry*
Reg. No./Substance:
0/Integrin alphaVbeta3; 0/Oligopeptides; 0/Organotechnetium Compounds; 0/Peptide Fragments; 0/Radiopharmaceuticals; 0/tat Gene Products, Human Immunodeficiency Virus; 0/tat peptide (49-57), Human immunodeficiency virus 1; 123491-58-7/arginine-glycine-aspartate-O-methyltyrosine amide

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