cRGD peptide-conjugated icosahedral closo-B12(2-) core carrying multiple Gd3+-DOTA chelates for α(v)ß3 integrin-targeted tumor imaging (MRI).
Inorg Chem
; 52(4): 1701-9, 2013 Feb 18.
Article
en En
| MEDLINE
| ID: mdl-23391150
ABSTRACT
A vertex-differentiated icosahedral closo-B(12)(2-) core was utilized to construct a α(v)ß(3) integrin receptor-targeted (via cRGD peptide) high payload MRI contrast agent (CA-12) carrying 11 copies of Gd(3+)-DOTA chelates attached to the closo-B(12)(2-) surface via suitable linkers. The resulting polyfunctional MRI contrast agent possessed a higher relaxivity value per-Gd compared to Omniscan, a small molecular contrast agent commonly used in clinical settings. The α(v)ß(3) integrin receptor specificity of CA-12 was confirmed via in vitro cellular binding experiments and in vivo MRI of mice bearing human PC-3 prostate cancer xenografts. Integrin α(v)ß(3)-positive MDA-MB-231 cells exhibited 300% higher uptake of CA-12 than α(v)ß(3)-negative T47D cells. Serial T1-weighted MRI showed superior contrast enhancement of tumors by CA-12 compared to both a nontargeted 12-fold Gd(3+)-DOTA closomer control (CA-7) and Omniscan. Contrast enhancement by CA-12 persisted for 4 h postinjection, and subsequent enhancement of kidney tissue indicated a renal elimination route similar to Omniscan. No toxic effects of CA-12 were apparent in any mice for up to 24 h postinjection. Post-mortem ICP-OES analysis at 24 h detected no residual Gd in any of the tissue samples analyzed.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias de la Próstata
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Imagen por Resonancia Magnética
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Quelantes
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Medios de Contraste
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Integrina alfaVbeta3
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Neoplasias Experimentales
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Inorg Chem
Año:
2013
Tipo del documento:
Article
País de afiliación:
Estados Unidos