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Investigation using an HER‐2/neu transgenic mouse model of a newly developed MR contrast agent with the effect of an antitumor drug
Authors:Akinaga Sonoda PhD  Norihisa Nitta PhD  Shinich Ohta PhD  Ayumi Nitta‐Seko MD  Satoshi Murata PhD  Jun‐ichiro Jo PhD  Yasuhiko Tabata PhD  Masashi Takahashi MD  Toru Tani PhD  Kiyoshi Murata PhD
Affiliation:1. Department of Radiology, Shiga University of Medical Science, Setatsukinowa‐cho, Otsu, Shiga, Japan;2. Department of Surgery, Shiga University of Medical Science, Setatsukinowa‐cho, Otsu, Shiga, Japan;3. Department of Biomaterials, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan
Abstract:

Purpose

To assess whether Gd‐DTPA‐Gel‐Cis, a conjugate of gadolinium (Gd), cis diamminedichloroplatinum (Cis), diethylenetriaminepentaacetic acid (DTPA)‐dianhydride, and bovine gelatin (Gel) can be used as an intravascular contrast agent at MRI and as an antitumor cell proliferation agent in vitro.

Materials and Methods

We injected Gd‐DTPA‐Gel‐Cis (200 mg/mL) into the caudal vein of female HER‐2/neu transgenic mice with spontaneous mammary tumors. The tumor signal intensity was measured with a 0.3 Tesla MRI scanner. HER‐2/neu‐expressing NT cells were treated with Gd‐DTPA‐Gel‐Cis (5 μM cisplatin, 200 mg/mL Gel), Cis alone (5 μM cisplatin), or Gel alone (200 mg/mL gelatin). Differences of P < 0.05 were considered to be statistically significant.

Results

On T1‐weighted MRI scans of mice injected with Gd‐DTPA‐Gel‐Cis we observed a 23% increase in signal intensity. The survival rates of cells exposed to Gd‐DTPA‐Gel‐Cis or Cis were 70.9% and 58.3%, respectively, of the survival rates observed after treatment with Gel alone. Gd‐DTPA‐Gel‐Cis showed significant toxicity (P < 0.05).

Conclusion

Gd‐DTPA‐Gel‐Cis shows promise for use as an MRI contrast medium and as an antitumor agent. J. Magn. Reson. Imaging 2009;30:907–910. © 2009 Wiley‐Liss, Inc.
Keywords:HER‐2/neu transgenic mice  gadolinium  cis diamminedichloroplatinum  diethylenetriaminepentaacetic acid  gelatin
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