Abstract 4545: Positron emission tomography (PET) of TSPO expression in preclinical models of human cancer

There is a critical need to develop and rigorously validate molecular imaging biomarkers to aid diagnosis and characterization of human cancer. Elevated expression of translocator protein (TSPO) has been shown to predict disease progression and aggressive, invasive behavior in a variety of solid tumors. Thus, noninvasive molecular imaging of TSPO expression could form the basis of a novel, predictive cancer imaging biomarker. In quantitative preclinical PET studies, we have evaluated a high-affinity pyrazolopyrimidinyl TSPO imaging ligand ([ 18 F]DPA-714) and an aryloxyanilide-based TSPO imaging ligand ([ 18 F]PBR06), as translational probes for quantification of TSPO levels in glioma, breast cancer, and colorectal cancer. In these studies, glioma-bearing rats or genetically engineered mice bearing spontaneously arrising breast or colorectal cancers were imaged with TSPO PET ligands in a microPET system. Dynamic images were acquired simultaneously upon injection of radioactive TSPO PET ligands. Arterial blood was collected to derive the input function (AIF), with HPLC radiometabolite analysis performed upon select samples for AIF correction. Compartmental modeling was performed using the corrected AIF. Immediately following imaging, tumor and healthy surrounding tissues were harvested for validation by western blotting and immunohistochemistry. Our results illustrate the feasibility of using TSPO PET ligands for visualization of TSPO-expressing tumors of the brain, breast and colon. Importantly, both [ 18 F]DPA-714 and [ 18 F]PBR06 appear suitable for quantitative assay of tumor TSPO levels in vivo. Given the relationship between elevated TSPO levels and poor outcome in oncology, these studies suggest the potential of these imaging agents to serve as a novel predictive cancer imaging biomarkers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4545. doi:1538-7445.AM2012-4545