Investigation using an HER-2/neu transgenic mouse model of a newly developed MR contrast agent with the effect of an antitumor drug.
OBJECTIVE
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.


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 microM cisplatin, 200 mg/mL Gel), Cis alone (5 microM 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).


CONCLUSIONS
Gd-DTPA-Gel-Cis shows promise for use as an MRI contrast medium and as an antitumor agent.
Sonoda
Akinaga
A
Department of Radiology, Shiga University of Medical Science, Setatsukinowa-cho, Otsu, Shiga, Japan. akinagasonoda@yahoo.co.jp
Nitta
Norihisa
N
Ohta
Shinich
S
Nitta-Seko
Ayumi
A
Murata
Satoshi
S
Jo
Jun-Ichiro
J
Tabata
Yasuhiko
Y
Takahashi
Masashi
M
Tani
Toru
T
Murata
Kiyoshi
K
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D002417:Cattle; D002945:Cisplatin / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D003287:Contrast Media / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D003432:Cross-Linking Reagents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D019786:Gadolinium DTPA / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D005780:Gelatin / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D018734:Genes, erbB-2; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008325:Mammary Neoplasms, Experimental / Q000175:diagnosis* / Q000188:drug therapy*; D051379:Mice; D008822:Mice, Transgenic
D000970:Antineoplastic Agents; D003287:Contrast Media; D003432:Cross-Linking Reagents; C545576:GD-DTPA-Gel-Cis; D005780:Gelatin; D019786:Gadolinium DTPA; D002945:Cisplatin