Comparison of Three Positron Emission Tomography Tracers in Murine Models of Malignant Mesothelioma

Abstract

Malignant mesothelioma is a highly aggressive tumor arising from mesothelial cells of the pleura and peritoneum. Although this used to be a rare tumor, the incidence is expected to increase worldwide over the next several decades. Current treatment of choice for mesothelioma is surgical resection, which may be combined with chemotherapy and/or radiation. However, the prognosis of patients after this multimodality therapy remains poor and median survival of patients from diagnosis ranges from 8 to 18 months. Thus, it is urgently necessary to establish new and more effective treatments. To develop new treatments, non-invasive imaging for evaluating the efficacy of new treatments is essential. A positron emission tomography (PET) using F-18 fluorodeoxyglucose (FDG) is widely applied for the diagnosis of various cancers. However, since FDG also accumulates in inflammatory lesions, FDG-PET may become falsely positive in post-treatment tumors complicated with reactive inflammatory changes, which limits the usefulness of FDG-PET in evaluating treatment response. F-18 fluorothymidine (FLT) and C-11 thiothymidine (S-dThd), which are analogs of thymidine and tracers for measuring nucleic acid metabolism, are reported to accumulate less in inflammatory lesions than FDG. In this study, we established orthotopic implantation models of malignant pleural mesothelioma in mice and compared three PET tracers for imaging in these models.