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Inorg Chem. 2013 Feb 18;52(4):1701-9. doi: 10.1021/ic302340c. Epub 2013 Feb 7.

cRGD peptide-conjugated icosahedral closo-B12(2-) core carrying multiple Gd3+-DOTA chelates for α(v)β3 integrin-targeted tumor imaging (MRI).

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1
International Institute of Nano and Molecular Medicine, School of Medicine, University of Missouri, Columbia, Missouri 65211-3450, United States.

Abstract

A vertex-differentiated icosahedral closo-B(12)(2-) core was utilized to construct a α(v)β(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)β(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)β(3)-positive MDA-MB-231 cells exhibited 300% higher uptake of CA-12 than α(v)β(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.

PMID:
23391150
PMCID:
PMC3593306
DOI:
10.1021/ic302340c
[Indexed for MEDLINE]
Free PMC Article
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