The Trans locator Protein Radioligand 18F-DPA-714 Monitors Antitumor Effect of Erufosine in a Rat 9L Intracranial Glioma Model

On the one hand, the translocator protein (TSPO) radioligand N, N-diethy1-2-(2-(4-(2-F-18-fluoroethoxy)phenyl)-5,7-dimethyl pyrazolo [1,5-a]pyrimidin-3-yl)acetamide (F-18-DPA-714) has been suggested to serve as an alternative radiotracer to image human glioma, and on the other hand the alkylphosphocholine erufosine (ErPC3) has been reported to induce apoptosis in otherwise highly apoptosis-resistant glioma cell lines. The induction of apoptosis by ErPC3 requires TSPO, a mitochondria] membrane protein highly expressed in malignant gliomas. In this preclinical study, we monitored the effect of ErPC3 treatment in vivo using F-18-DPA-714 PET. Methods: In vitro studies investigated the antitumor effect of ErPC3 in 9L rat gliosarcoma cells. In vivo, glioma-bearing rats were imaged with F-18-DPA-714 for the time of treatment. Results: A significant decrease in 9L cell proliferation and viability and a significant increase in apoptosis and caspase-3 activation were demonstrated on ErPC3 treatment in cell culture. In the rat model, ErPC3 administration resulted in significant changes in F-18-DPA-714 tumor uptake over the course of the treatment. Immunohistochemistry revealed reduced tumor volume and increased cell death in ErPC3-treated animals accompanied by infiltration of the tumor core by CD11b-positive microglia/macrophages and glial fibrillary acidic protein positive astrocytes. Conclusion: Our findings demonstrate a potent antitumor effect of ErPC3 in vitro, in vivo, and ex vivo. PET imaging of TSPO expression using F-18-DPA-714 allows effective monitoring and quantification of disease progression and response to ErPC3 therapy in intracranial 9L gliomas.