cRGD Peptide-Conjugated Icosahedral closo-B122- Core Carrying Multiple Gd3+-DOTA Chelates for 伪v尾3 Integrin-Targeted Tumor Imaging (MRI)

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• 作者：Lalit N. Goswami ; Lixin Ma ; Quanyu Cai ; Saurav J. Sarma ; Satish S. Jalisatgi ; M. Frederick Hawthorne
• 刊名：Inorganic Chemistry
• 出版年：2013
• 出版时间：February 18, 2013
• 年：2013
• 卷：52
• 期：4
• 页码：1701-1709
• 全文大小：472K
• 年卷期：v.52,no.4(February 18, 2013)
• ISSN：1520-510X

文摘

A vertex-differentiated icosahedral closo-B₁₂^2- core was utilized to construct a 伪_v尾₃ integrin receptor-targeted (via cRGD peptide) high payload MRI contrast agent (CA-12) carrying 11 copies of Gd³⁺-DOTA chelates attached to the closo-B₁₂^2- 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 伪_v尾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 伪_v尾₃-positive MDA-MB-231 cells exhibited 300% higher uptake of CA-12 than 伪_v尾₃-negative T47D cells. Serial T1-weighted MRI showed superior contrast enhancement of tumors by CA-12 compared to both a nontargeted 12-fold Gd³⁺-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.