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In Vitro Demonstration of Synergy Between Radionuclide and Chemotherapy

Groupe de Recherche en Médecine Nucléaire, Centre E Marquis, and Institut National de la Santé et de la Recherche Médicale Unité 49, Hôpital Pontchaillou, Rennes, France

Correspondence: For correspondence or reprints contact: Jean-Luc Raoul, MD, PhD, Centre E Marquis, rue de la Bataille Flandres, Dunkerque BP 6279, Rennes Cedex, 35062 France.

ABSTRACT

Radionuclide therapy is currently used in the treatment of some malignancies, including hepatocellular carcinoma. The effects of external beam radiotherapy are improved by combining it with chemotherapy. The aim of this study was to determine whether such a synergistic effect could be demonstrated in vitro with internal radiation therapy. Methods: HepG2 cells were cultured from Day 0 to Day 8 under the following conditions: exposure for 4 hr on Day 2 to increasing concentrations of 5-fluorouracil (5FU), doxorubicin orcisplatin (CDDP); exposure from Day 2 to Day 8 to increasing concentrations of ¹³¹-Iiodide; exposure on Day 2 to low-toxicity doses of drugs for 4 hr, followed by exposure to ¹³¹I at increasing concentrations; and exposure to increasing concentrations of ¹³¹I from Day 2 to Day 8, with exposure for 4 hr on Day 6 to the drugs. Cell toxicity was assessed by enzyme release (lactate dehydrogenase and aspartate aminotransferase) in the culture medium and on cell survival (protein and tetrazolium dye test). All cultures were run in triplicate. Results: A dose-and time-dependent toxicity was demonstrated with doxorubicin and CDDP but not with 5FU. When HepG2 cells were exposed to ¹³¹I, the toxicity was rather low, but significant, and was time- and dose-dependent. Treating these cells with combination radiotherapy and chemotherapy resulted in a toxicity that was significantly greater than that with ¹³¹I or chemotherapy drugs alone. Conclusion: The radiosensitivity of HepG2 cells is low; combining a chemotherapeutic drug with a radiotherapeutic agent improves the radiosensitivity in a synergistic fashion. This combination is thus able to strengthen the therapeutic effect of internal radiation therapy in different malignancies, particularly in hepatocellular carcinoma.

Key Words: radionuclidetherapy • iodine-131 • chemoradiotherapy

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