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Combination ¹⁸⁶Re-HEDP and Cisplatin Supra-Additive Treatment Effects in Prostate Cancer Cells

Departments of Nuclear Medicine and Urology, Academisch Ziekenhuis Vrije Universiteit, Amsterdam, The Netherlands

Correspondence: For correspondence or reprints contact: Albert A. Geldof, PhD, Department of Nuclear Medicine and Department of Urology, Academisch Ziekenhuis Vrije Universiteit, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands.

ABSTRACT

Radionuclide therapy has proven to be an efficacious palliative treatment for metastatic prostate cancer. Its potential therapeutic possibilities may be substantially increased by combining it with effective radiosensitizing drugs. Methods: This study explores the radiosensitizing properties of cisplatin when combined with ¹⁸⁶Re-labeled hydroxyethylidene diphosphonate (HEDP) in the treatment of R3327-MATLyLu prostate cancer cells in vitro. A concomitant incubation during 4 d, combining various concentrations of cisplatin (0, 0.42, 0.83 and 1.67 µmoI/L) and ¹⁸⁶Re-HEDP (0, 1.84 and 3.69 MBq/mL [0, 50 and 100 µCi/mL, respectively]) was followed by the determination of the cell numbers surviving and the replating of these cells in semisolid agar. Results: The surviving fraction of clonogenic tumor cells after combination treatment clearly showed synergism when analyzed by a panel of three different published analytical methods. In addition, analysis of variance demonstrated a significant interaction between radionuclide therapy and cisplatin-based chemotherapy (P < 0.001). Treatment with ¹⁸⁶Re-HEDP and cisplatin by sequential incubation yielded similar, but never superior results. Conclusion: It is concluded that radionuclide therapy in combination with cisplatin is able, in principle, to improve therapeutic success rate in metastatic prostate cancer in a more than additive way.

Key Words: synergism • combination therapy • prostate cancer • in vitro • ¹⁸⁶Re-hydroxyethylidene diphosphonate

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