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Combined Tumor Therapy by Using Radiofrequency Ablation and 5-FU–Laden Polymer Implants: Evaluation in Rats and Rabbits¹

John R. Haaga, MD, Agata A. Exner, PhD, Yadong Wang, PhD, Nicholas T. Stowe, PhD and Peter J. Tarcha, PhD

¹ From the Department of Radiology, University Hospitals of Cleveland and Case Western Reserve University, 11100 Euclid Ave, Cleveland, OH 44106-5056 (J.R.H., A.A.E., N.T.S.); Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Mass (Y.W.); and Department of Advanced Drug Delivery, Abbott Laboratories, North Chicago, Ill (P.J.T.). Received November 18, 2004; revision requested January 6, 2005; revision received February 11; accepted March 15. Address correspondence to A.A.E. (e-mail: Exner{at}uhrad.com).

PURPOSE: To evaluate the use of 5-fluorouracil (5-FU)-laden polymer implants as an adjunct to radiofrequency (RF) ablation for tumor treatment.

MATERIALS AND METHODS: All animal studies were performed in compliance with the Case Western Reserve University Institutional Animal Care and Use Committee guidelines. Three studies were performed to investigate (a) in vitro dissolution of 5-FU–laden polymer implants in saline and bovine serum, (b) tissue distribution of 5-FU and its metabolite, 5-fluorouridine (5-FUrd), in the ablated liver tissue of rats (n = 4), and (c) efficacy of combined approach (n = 4) compared with that of ablation alone (n = 6) for VX2 liver tumor model in rabbits. Characterization of 5-FU release in vitro and distribution of 5-FU in rat liver tissue were analyzed by using high performance liquid chromatography; in vivo efficacy was assessed by using computed tomography and pathologic examination.

RESULTS: Results of the in vitro dissolution study showed that a 75% release of 5-FU occurred in 2 days when exposed to bovine serum and in 9 days when exposed to phosphate-buffered saline. In the ablated rat liver, the 5-FU level was higher at the center and lower at the periphery of the tissue both at 24 hours (41.0 mg per kilogram tissue vs 15.0 mg per kilogram tissue, respectively) and at 48 hours (8.0 mg per kilogram tissue vs 2.0 mg per kilogram tissue, respectively). The 5-FUrd concentration was twofold higher peripherally than centrally and was higher at 48 hours than at 24 hours. In rabbits, local delivery of 5-FU immediately after RF ablation provided a significant (P < .05) reduction in tumor size compared with ablation alone (1.80 cm³ ± 0.28 [standard error] vs 3.53 cm³ ± 0.52, respectively; P = .034) and a more than 20-fold reduction in tumor size compared with the control (1.80 cm³ ± 0.28 vs 41.95 cm³ ± 11.58, respectively; P = .018).

CONCLUSION: Combined treatment by using 5-FU polymer implants and RF ablation shows uniform sustained release of 5-FU for 48 hours at least 8 mm from the edge of the ablation zone and appears to be successful at controlling the growth of an experimental tumor in rabbits appreciably better than does ablation alone.

© RSNA, 2005

This article has been cited by other articles:

				B. D. Weinberg, T. M. Krupka, J. R. Haaga, and A. A. Exner Combination of Sensitizing Pretreatment and Radiofrequency Tumor Ablation: Evaluation in Rat Model Radiology, March 1, 2008; 246(3): 796 - 803. [Abstract] [Full Text] [PDF]