Abstract
Malignant mesothelioma (MM) is a highly aggressive tumor arising from serosal surfaces of the pleura/peritoneum caused by asbestos exposure. MM has three histological types, epithelioid, sarcomatoid and mixed, and its incidence is expected to increase. 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) and X-ray radiotherapy (XRT) for MM in mouse models. We inoculated human epithelioid and sarcomatoid MM cells 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). Although the sizes of xenografts with CIRT (30 Gy) or XRT (60 Gy) increased until 2 weeks after irradiation in both tumor types, those turned to reduce thereafter. Pathological analysis showed increased cell death at 7 days after irradiation and increased fibrosis at 14 days. To determine whether the efficacy of treatment is 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 after CIRT and XRT. 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 the therapeutic efficacy of CIRT was twice as high as XRT in both types of mesothelioma. FLT-PET would be useful for the early assessment of treatment response in epithelioid tumors, but suitable tracer remains to be determined for sarcomatoid tumors.
