期刊
EUROPEAN JOURNAL OF RADIOLOGY
卷 73, 期 2, 页码 420-427出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.ejrad.2008.11.025
关键词
Integrin alphavbeta3/metabolism; Arg-Gly-Asp; RGD peptides; Nude mice; Magnetic resonance imaging/methods; Hepatocellular carcinoma/neoplasms
资金
- Peking University People's Hospital
- Department of Radiology, Peking University People's Hospital
Rationale and objective: The aim of this study is to develop a novel MR probe containing arginine-glycine-aspartic acid (RGD) motif for imaging integrin on alpha nu beta 3 receptor-expressed tumor. Materials and methods: Commercially available HYNIC-RGD conjugated with co-ligand EDDA was labeled with Gd3+, and the mixture was isolated and purified by solid phase extract (SPE) to get the entire probe Gd-EDDA/HYNIC-RGD. Human hepatocellular carcinoma (HHCC) cell line BEL-7402 was cultured and the cells harvested and suspended in serum-free Dulbecco's modified Eagle medium (DMEM) were subcutaneously inoculated into athymic nude mice for tumor growth. In vitro cell binding assay to integrin alpha nu beta 3 receptor and cell viability experiments were conducted. The in vivo imaging of the three arms of xenografts were performed by MR scan with a dedicated animal coil at time points of 0, 30, 60, 90 min and 24-h post-intravenous injection (p.i.). Three arms of nude mice then were sacrificed for histological examination to confirm the imaging results. Results: Gd-EDDA/HYNIC-RGD was successfully isolated by SPE and validity was verified on signal enhancement through in vitro and in vivo experiments. The nude mice model bearing HHCC was well established. There was approx. 30% signal enhancement on T1WI FSE images at 90 min post-intravenous injection of the Gd-EDDA/HYNIC-RGD compared with baseline, and the signal to time curve is straightforward over time in the span of 0-90 min p.i., while the control arms do not show this tendency. Conclusion: Gd-EDDA/HYNIC-RGD has the potential to serve as an MR probe detecting integrin alpha nu beta 3 receptor-expressed tumor. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
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