Gd-EDDA/HYNIC-RGD as an MR molecular probe imaging integrin alphanubeta3 receptor-expressed tumor-MR molecular imaging of angiogenesis.
OBJECTIVE
The aim of this study is to develop a novel MR probe containing arginine-glycine-aspartic acid (RGD) motif for imaging integrin alphanubeta3 receptor-expressed tumor.


METHODS
Commercially available HYNIC-RGD conjugated with co-ligand EDDA was labeled with Gd(3+), 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 alphanubeta3 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, 90min 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 90min 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 0-90min p.i., while the control arms do not show this tendency.


CONCLUSIONS
Gd-EDDA/HYNIC-RGD has the potential to serve as an MR probe detecting integrin alphanubeta3 receptor-expressed tumor.
Huo
Tianlong
T
Peking University People's Hospital, Radiology Department, 11 Xizhimen South Street, Xicheng District, Beijing 100044, China. huotianlong@bjmu.edu.cn
Du
Xiangke
X
Zhang
Sen
S
Liu
Xia
X
Li
Xubing
X
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000378:metabolism; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000737:chemistry; D004048:Diethylamines / Q000737:chemistry; D005682:Gadolinium / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D006834:Hydrazines / Q000737:chemistry; D007089:Image Enhancement / Q000379:methods*; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D015336:Molecular Probe Techniques; D009389:Neovascularization, Pathologic / Q000175:diagnosis* / Q000378:metabolism*; D009539:Nicotinic Acids / Q000737:chemistry; D009842:Oligopeptides / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
C120392:6-hydrazinopyridine-3-carboxylic acid; D003287:Contrast Media; D004048:Diethylamines; D006834:Hydrazines; D039302:Integrin alphaVbeta3; D009539:Nicotinic Acids; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; D005682:Gadolinium; C492592:2,2'-(ethylenedioxy)diethylamine