Enhanced antitumor effect of tirapazamine delivered intraperitoneally to VX2 liver tumor-bearing rabbits subjected to transarterial hepatic embolization.

PURPOSE: We evaluated the effects of the combination of Tirapazamine (TPZ), activated preferentially under hypoxic conditions, and gelatin microspheres (GMS) on the tumor growth ratio in rabbits. METHODS: We assigned 20 liver tumor-bearing Japanese white rabbits to 4 equal groups. Group 1 received 1 ml of saline intra-arterially (i.a.) and 20 ml of saline intraperitoneally (i.p.; saline group). Group 2 was injected with GMS i.a. and 20 ml saline i.p. (GMS group). Group 3 received 1 ml of saline i.a. and 300 mg/m(2) of TPZ i.p. (TPZ group), and group 4 was treated with GMS i.a. and 300 mg/m(2) of TPZ i.p. (GMS + TPZ group). The infusion of GMS was stopped when the blood flow stagnated. Before and 7 days after treatment, the liver tumor volumes were measured as the total number of pixels on 0.3Tesla (T) magnetic resonance imaging (MRI) scans. RESULTS: The tumor growth ratio (mean ± standard deviation) of the saline, GMS, TPZ, and GMS + TPZ groups was 519.15 ± 93.78, 279.24 ± 91.83, 369.78 ± 95.73, and 119.87 ± 17.62, respectively. The difference between the GMS + TPZ group and the other groups was statistically significant (P < 0.05). CONCLUSIONS: Our results show that the combination of TPZ i.p. and GMS i.a. enhanced the antitumor effect of TPZ. This procedure may represent a new alternative treatment for patients with hepatic cell carcinoma.

The Possibility of differentiation between nonalcoholic steatohepatitis and fatty liver in rabbits on Gd-EOB-DTPA-enhanced open-type MRI scans.

RATIONALE AND OBJECTIVES: We used rabbits to investigate the possibility of differentiating between nonalcoholic steatohepatitis (NASH) and fatty liver (FL) on scans acquired by open-type‒ and gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)‒enhanced magnetic resonance imaging (MRI). MATERIALS AND METHODS: We divided 15 adult rabbits into three equal groups; they received standard (control group), high-fat (FL) content (FL group), or choline-deficient chow (NASH group). With the animals under general anesthesia we acquired scans on an open 0.3-Tesla MRI system. Signal intensity (SI) was measured before and after contrast administration and defined as SI-pre and SI-post, respectively. Relative SI enhancement (Sr) was calculated using the equation: Sr = (average of three SI-post- minus average of three SI values in no-signal fields)/(average of three SI-pre- minus average of three SI values in no-signal fields) × 100. Maximum Sr (Srmax), the time (in seconds) required to reach Srmax (Tmax), and the difference between Srmax and Sr at 30 minutes (Sr(30m)R) were analyzed. RESULTS: Srmax was significantly higher in the NASH rabbits than the other two groups (P < .05). CONCLUSIONS: In rabbits, the Srmax value made it possible to differentiate NASH from normal and fatty liver.

Complex comprised of dextran magnetite and conjugated cisplatin exhibiting selective hyperthermic and controlled-release potential.

We developed a dextran-magnetite conjugated cisplatin (DM-Cis) complex for use in thermal ablation and as a chemotherapeutic drug. To produce DM-Cis we reacted Cis with 1 mL DM (56 mg/mL iron). The temperature rise of DM-Cis was measured in vitro and in vivo under a portable induction-heating (IH) device. Platinum desorption from DM-Cis over 24 hours was measured in bovine serum. In in vivo accumulation and magnet and exothermic experiments we used four rat groups. In group 1 we delivered DM-Cis intraperitoneally (ip) and placed magnets subcutaneously (sc). In group 2 we injected saline (ip) and placed magnets (sc). In group 3 we injected DM-Cis (ip) and placed a sc incision (sham). The control (group 4) received an ip injection of saline. Rectus abdominis muscle tissue was stained with hematoxylin-eosin and iron-stained tissue areas (µm(2)) were calculated. The maximum platinum concentration in DM-Cis was approximately 105.6 µg/mL. Over 24 hours, 33.48% of platinum from DM-Cis was released. There was a significant difference (P < 0.05) in the iron-stained area between group 1 and the other groups. The temperature in muscle tissue registered a maximum of 56°C after about 4 min. DM-Cis may represent a magnetically-accumulated anticancer drug with hyperthermic effects.

Controlled release and antitumor effect of pluronic F127 mixed with cisplatin in a rabbit model.

The purpose of this study was to evaluate pluronic F127 for the controlled release of cisplatin in a rabbit model. Pluronic F127 becomes liquid at temperatures <25 degrees C and converts to a gelatinous state at temperatures between 25 and 60 degrees C. Six Japanese white rabbits were injected with pluronic + cisplatin (n = 3, renal group A) or saline + cisplatin (n = 3, renal group B) to measure the platinum concentration in kidneys. Another 25 rabbits with VX2 liver tumors were divided into five equal groups. They were injected with saline, saline + cisplatin, iodized oil + cisplatin, pluronic alone, or pluronic + cisplatin and labeled as liver groups A, B, C, D, and E, respectively. The antitumor effect of pluronic was then assessed. In the presence of pluronic, the platinum concentration in the kidneys of rabbits remained relatively high. In animals with liver tumors, the delivery of pluronic + cisplatin produced higher tumor reduction rates (P < 0.05) than in the other groups, without apparent damage to normal liver tissue. We conclude that pluronic is useful for the controlled release of cisplatin in a rabbit model.

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

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 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). CONCLUSION: Gd-DTPA-Gel-Cis shows promise for use as an MRI contrast medium and as an antitumor agent.