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Combination of Sensitizing Pretreatment and Radiofrequency Tumor Ablation: Evaluation in Rat Model¹

¹ From the Departments of Biomedical Engineering (B.D.W., T.M.K.) and Radiology (T.M.K., J.R.H., A.A.E.), Case Western Reserve University, 11100 Euclid Ave, Cleveland, OH 44106-5056. Received February 2, 2007; revision requested April 5; revision received May 9; accepted June 11; final version accepted July 31. A.A.E. supported by National Institutes of Health grants R21 EB002847 and R01 CA118399. B.D.W. supported in part by National Institutes of Health grant T32 GM07250 to the Case Western Reserve University Medical Scientist Training Program and by Department of Defense predoctoral fellowship BC043453. Address correspondence to A.A.E. (e-mail: agata.exner{at}case.edu).

Purpose: To prospectively determine, in an animal tumor model, if the block copolymer Pluronic P85 (BASF, Shreveport, La) sensitizes cancer cells to hyperthermia and if intratumorally or intravenously administered copolymer improves the therapeutic outcome of radiofrequency (RF) ablation tumor treatment.

Materials and Methods: The effects of Pluronic P85 and mild hyperthermia in vitro were tested in DHD/K12/TRb rat colorectal carcinoma cells. Cells were incubated at 37°C or 43°C for 15–60 minutes with 0%, 7%, or 10% wt/wt Pluronic P85, and cell viability was assessed by using a mitochondrial enzyme assay. In vivo experiments were performed as approved by the Institutional Animal Care and Use Committee at Case Western Reserve University and according to all applicable guidelines on animal use. Bilateral subcutaneous tumors in rats were treated with either intratumoral (13 tumors) or intravenous (15 tumors) Pluronic P85 followed by ablation or with ablation alone (14 tumors) and were monitored for 14 days by using volumes estimated from caliper measurements of tumor diameter. Acute effects of Pluronic P85 on the size of ablation-induced coagulation were measured after 24 hours in additional tumors (six tumors each treated according to the protocol for the ablation-only, intratumoral injection, and intravenous injection groups). Statistical testing was performed by using linear regression analysis and two-sided t tests with a significance level of .05.

Results: At 43°C, 7% and 10% Pluronic P85 reduced in vitro cell viability by 22% ± 5 (standard error of the mean) (P < .001) and 28% ± 5 (P < .001), respectively, compared with the viability of control cells. At day 14, the volume of tumors ablated after local and systemic Pluronic P85 pretreatment changed by –55% ± 14 (P = .03) and –59% ± 14 (P = .02), respectively, compared with an increase of 16% ± 28 for tumors treated with ablation alone. Coagulation area at 24 hours was reduced by 44% relative to that in control tumors (P = .03) after intratumoral Pluronic P85 but was unchanged after systemic Pluronic P85.

Conclusion: Tumor pretreatment with Pluronic P85 improved the outcome of RF ablation by decreasing the tumor volume and residual tumor in an experimental carcinoma model.

© RSNA, 2008