title: cRGD peptide-conjugated icosahedral closo-B12(2-) core carrying multiple Gd3+-DOTA chelates for α(v)β3 integrin-targeted tumor imaging (MRI).
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.
authors: International Institute of Nano and Molecular Medicine, School of Medicine, University of Missouri, Columbia, Missouri 65211-3450, United States.
authors: Lalit N
authors: LN
authors: Goswami
authors: Lixin
authors: L
authors: Ma
authors: Quanyu
authors: Q
authors: Cai
authors: Saurav J
authors: SJ
authors: Sarma
authors: Satish S
authors: SS
authors: Jalisatgi
authors: M Frederick
authors: MF
authors: Hawthorne
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry; D003287:Contrast Media / Q000138:chemical synthesis / Q000737:chemistry; D005682:Gadolinium / Q000737:chemistry; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000096:biosynthesis / Q000737:chemistry*; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D016513:Mice, SCID; D015394:Molecular Structure; D009374:Neoplasms, Experimental / Q000175:diagnosis*; D010456:Peptides, Cyclic / Q000737:chemistry; D011471:Prostatic Neoplasms / Q000175:diagnosis*; D014805:Vitamin B 12 / Q000737:chemistry
chemical_list: D002614:Chelating Agents; D003287:Contrast Media; D006573:Heterocyclic Compounds, 1-Ring; D039302:Integrin alphaVbeta3; D010456:Peptides, Cyclic; C507169:cyclic arginine-glycine-aspartic acid peptide; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D005682:Gadolinium; D014805:Vitamin B 12
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