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Experimental Studies |
1 From the Depts of Radiology (W.L.M., J.B.K., M.A., J.C.H., S.N.G.) and Medical Oncology (K.E.S.), Beth Israel Deaconess Med Ctr, Harvard Med School, 330 Brookline Ave, Boston, MA 02215; Dept of Pharmaceutical Sciences, Bouve College of Health Sciences, Northeastern Univ, Boston, Mass (A.N.L., V.P.T.); Dept of Cancer Biology, Dana-Farber Cancer Inst, Boston, Mass (G.D.G.); and Dept of Radiology, Massachusetts Gen Hosp, Boston, Mass (G.S.G.). Received Aug 23, 2001; revision requested Oct 11; final revision received Feb 27, 2002; accepted Mar 28. Supported in part by grants from Radionics, Burlington, Mass. Address correspondence to S.N.G. (e-mail: sgoldber@caregroup.harvard.edu).
PURPOSE: To determine whether intratumoral accumulation of liposomal doxorubicin or free unencapsulated doxorubicin is increased when combined with radio-frequency (RF) ablation.
MATERIALS AND METHODS: Two 1.2–1.5-cm R3230 mammary adenocarcinomas were grown within the mammary fat pads of 19 female Fischer rats. One tumor of each pair was treated with RF ablation (tip temperature, 70°C ± 2 [SD]; 120 mA ± 75) for 5 minutes, whereas the other tumor was a control. Intravenous liposomal doxorubicin (1 mg in 500 µL, n = 6) or intravenous free unencapsulated doxorubicin (n = 7) was administered immediately following RF ablation. Doxorubicin was extracted in acid alcohol from tumors 24 hours following RF ablation, and fluorescent spectrophotometry was used to quantify extracted doxorubicin. Comparisons of intratumoral doxorubicin accumulation in tumors treated with RF ablation and in untreated tumors were analyzed with parametric (paired Student t test) and nonparametric (Wilcoxon rank sum test) statistics. Findings at autoradiography with densitometry (six additional tumors) demonstrated the spatial distribution of the intratumoral accumulation of liposomal doxorubicin.
RESULTS: When RF ablation preceded administration of liposomal doxorubicin, mean intratumoral doxorubicin concentration was 5.6 µg/g ± 2.1 (range, 1.9–7.7 µg/g), whereas 1.0 µg/g ± 0.4 (range, 0.5–1.5 µg/g) was present in control tumors not treated with RF ablation (P < .05). Thus, there was a mean 7.1-fold ± 4.9 increase in intratumoral doxorubicin accumulation following RF ablation (range, 2.1–14.5-fold) compared with the amount without RF pretreatment (P < .05). Increased intratumoral accumulation was not seen in animals receiving free doxorubicin with (mean, 0.4 µg/g ± 0.1) or without (mean, 0.8 µg/g ± 0.4) RF pretreatment (P = .07). Autoradiographic findings demonstrated accumulation of liposomal doxorubicin in a peripheral rim of tumor adjacent to the zone of coagulation.
CONCLUSION: RF ablation augments the delivery of systemic antineoplastic agents such as liposomal doxorubicin.
© RSNA, 2002
Index terms: Animals • Chemotherapy • Hyperthermia • Liposomes • Neoplasms • Radiofrequency (RF) ablation
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