Abstract
Malignant mesothelioma (MM) is a highly aggressive tumor arising from the pleura/peritoneum caused by asbestos exposure. Since the prognosis of patients remains poor after combined treatment with surgery, chemotherapy and radiation, it is important to develop more effective treatments. Thus, we evaluated the efficacy of carbon-ion radiotherapy (CIRT) having higher relative biological effectiveness than X-ray (XRT) in mouse models of MM. Human epithelioid and sarcomatoid MM cells were inoculated subcutaneously into nude mice. Xenografts were irradiated with 2-30 Gy of carbon ions (290 MeV/u, a 6-cm SOBP), or 5-60 Gy of X-ray (200 kVp, 20 mA). The sizes of xenografts with CIRT (30 Gy) or XRT (60 Gy) increased until 2 weeks after irradiation in both tumor types, but turned to reduce thereafter and disappeared. To determine whether the treatment efficacy can be evaluated before size reduction, we measured tumor uptake of 14C-FDG and 3H-FLT after CIRT (30 Gy) or XRT (60 Gy). In epithelioid tumors, FLT uptake decreased at 3 h and 1 day, but re-increased at 7 days after CIRT and XRT, correlating with the result of Ki-67 immunostaining. In sarcomatoid tumors, FLT uptake decreased with time after XRT, but it did not change after CIRT. FDG uptake was not correlated with efficacy of both treatments. These results indicated that CIRT was more effective for both types of mesothelioma than XRT, and FLT-PET, but not FDG, could be useful for the early assessment of treatment response in epithelioid tumors.
