Abstract
Radioiodine therapy has long been used for distant metastases of thyroid cancer. Although partially effective in most cases, it can render a complete cure only in a limited number of patients. One way to enhance its efficacy would be to combine it with antineoplastic agents. Here we describe an initialin vitro evaluation with 4 thyroid cancer cell lines.Methods: Cells were sparsely seeded in microtiter plates and allowed to grow for 2 days; then they were exposed to sublethal concentrations of cisplatin (CDDP), doxorubicin (Dox), or 5-fluorouracil (5-FU), followed by treatment with I-131 for 48 hr. Cell survival was measured with a commercial kit based on the colorimetry of succinate dehydrogenase activity.Results: Chemotherapeutic drugs exerted similar concentration-dependent cytotoxic effects in all 4 cell lines. The doses necessary to reduce the surviving fraction to half of the control were about 3 μg/ml for CDDP, 0.3 μg/ml for Dox, and 3 μg/ml for 5-FU (when used continuously for 48 hours). On the other hand, sensitivity to I-131 irradiation differed among the lines; same doses (7.4–14.8 MBq/ml) caused the greatest damage in FRO cells, a modest effect in NPA and WRO, and only minimal change in B-CPAP. The combined effect was most demonstrable in wells treated with Dox and radioiodine, whereas the addition of CDDP or 5-FU had marginal or insignificant merit, respectively. In FRO cells, half-lethal doses of the above mentioned CDDP, Dox, and 5-FU, when used together with 14.8 MBq/ml I-131, reduced cell survival to 54.5%, 29.4% and 33.4%, respectively, vs. 60.2% with radioiodine alone.Conclusion: In vitro, clinical concentrations of Dox can accelerate the killing of thyroid cancer cells by radioiodine. These favorable experimental results warrant future studies to evaluate whether this new bidisciplinary approach is clinically relevant and feasible.
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Schlumberger M, Challeton C, De Vathaire F, Travagli J-P, Gardet P, Lumbroso J-D, et al. Radioactive iodine treatment and external radiotherapy for lung and bone metastases from thyroid carcinoma.J Nucl Med 1996; 37: 598–605.
Kasagi K, Misaki T, Alam S, Konishi J. Radioiodine treatment for thyroid cancer.Thyroidol Clin Exp 1998; 10: 115–120.
Menzel C, Grünwald F, Schomburg A, Palmedo H, Bender H, Späth G, et al. “High-dose” radioiodine therapy in advanced differentiated thyroid carcinoma.J Nucl Med 1996; 37: 1496–1503.
Byfield JE. 5-Fluorouracil radiation sensitization—a brief review.Invest New Drugs 1989; 7: 111–116.
Vokes EE, Weichselbaum RR. Concomitant chemoradiotherapy: rationale and clinical experience in patients with solid tumors.J Clin Oncol 1990; 8: 911–934.
Wheeler RH, Spencer S. Cuisplatin plus radiation therapy.J Infus Chemother 1995; 5: 61–66.
Morris JC, Kim CK, Padilla ML, Mechanick JI. Conversion of non-iodine-concentrating differentiated thyroid carcinoma metastases into iodine-concentrating foci after anticancer chemotherapy.Thyroid 1997; 7: 63–66.
Venkataraman GM, Yatin M, Marcinek R, Ain KB. Restoration of iodide uptake in dedifferentiated thyroid carcinoma: relationship to human Na+/I− symporter gene methylation status.J Clin Endocrinol Metab 1999; 84: 2449–2457.
Estour B, Van Herle AJ, Juillard GJF, Totanes TL, Sparkes RS, Giuliano AE, et al. Characterization of a human follicular thyroid carcinoma cell line (UCLA RO 82 W-1).Virchows Archiv B Cell Pathol 1989; 57: 167–174.
Fagin JA, Matsuo K, Karmakar A, Chen DL, Tang SH, Koeffler HP. High prevalence of mutations of the p53 gene in poorly differentiated thyroid carcinomas.J Clin Invest 1993; 91: 179–184.
Fabien N, Fusco A, Santoro M, Barbier Y, Dubois P-M, Paulin C. Description of a human papillary thyroid carcinoma cell line.Cancer 1994; 73: 2206–2212.
Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays.J Immunol Methods 1983; 65: 55–63.
Denizot F, Lang R. Rapid colorimetric assay for cell growth and survival: modifications to the tetrazolium dye procedure giving improved sensitivity and reliability.J Immunol Methods 1986; 89: 271–277.
Ishiyama M, Shiga M, Sasamoto K, Mizoguchi M, He P. A new sulfonated tetrazolium salt that produces a highly water-soluble formazan dye.Chem Pharm Bull 1993; 41: 1118–1122.
Shimaoka K, Schoenfeld DA, DeWys WD, Creech RH, DeConti R. A randomized trial of doxorubicin versus doxorubicin plus cisplatin in patients with advanced thyroid carcinoma.Cancer 1985; 56: 2155–2160.
Williams SD, Birch R, Einhorn LH. Phase II evaluation of doxorubicin plus cisplatin in advanced thyroid cancer: A southeastern cancer study group trial.Cancer Treat Rep 1986; 70: 405–407.
Kim JH, Leeper RD. Treatment of locally advanced thyroid carcinoma with combination doxorubicin and radiation therapy.Cancer 1987; 60: 2372–2375.
Behr TM, Wulst E, Radetzky S, Blumenthal RD, Dunn RM, Gratz S, et al. Improved treatment of medullary thyroid cancer in a nude mouse model by combined radioimmunochemotherapy: doxorubicin potentiates the therapeutic efficacy of radiolabeled antibodies in a radioresistant tumor type.Cancer Res 1997; 57: 5309–5319.
Kievit E, Pinedo HM, Schlüper HMM, Boven E. Addition of cisplatin improves efficacy of131I-labeled monoclonal antibody 323/A3 in experimental human ovarian cancer.Int J Radiat Oncol Biol Phys 1997; 38: 419–428.
Chenoufi N, Raoul J-L, Lescoat G, Brissot P, Bourguet P.In vitro demonstration of synergy between radionuclide and chemotherapy.J Nucl Med 1998; 39: 900–903.
Matsushima Y, Kanzawa F, Hoshi A, Shimizu E, Nomori H, Sasaki Y, et al. Time-schedule dependency of the inhibiting activity of various anticancer drugs in the clonogenic assay.Cancer Chemother Pharmacol 1985; 14: 104–107.
Samuel AM, Rajashekharrao B. Radioiodine therapy for well-differentiated thyroid cancer: A quantitative dosimetric evaluation for remnant thyroid ablation after surgery.J Nucl Med 1994; 35: 1944–1950.
ICRP Publication No. 38. Radionuclide transformations: energy and intensity of emissions.Annals of ICCP 1983; 11–13: 452–453.
Nederman T. Effects of vinblastine and 5-fluorouracil on human glioma and thyroid cancer cell monolayers and sphenoids.Cancer Res 1984; 44: 254–258.
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Part of this article was presented at the 48th Annual Meeting of the Society of Nuclear Medicine, Toronto, Canada, June 23–27, 2001.
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Misaki, T., Iwata, M., Iida, Y. et al. Chemo-radionuclide therapy for thyroid cancer: Initial experimental study with cultured cells. Ann Nucl Med 16, 403–408 (2002). https://doi.org/10.1007/BF02990078
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DOI: https://doi.org/10.1007/BF02990078