Quantitative, Preclinical PET of Translocator Protein Expression in Glioma Using 18F-N-Fluoroacetyl-N-(2,5-Dimethoxybenzyl)-2-Phenoxyaniline

Translocator protein (TSPO) is a crucial 18 kDa outer mitochondrial membrane protein involved in numerous cellular functions, including regulation of cholesterol metabolism, steroidogenesis, and apoptosis. Elevated expression of TSPO in oncology correlates with disease progression and poor survival, suggesting that molecular probes capable of assaying TSPO levels may have potential as cancer imaging biomarkers. In preclinical PET imaging studies, we characterized a high-affinity aryloxyanilide-based TSPO imaging ligand, [18F]PBR06, as a candidate probe for quantitative assessment of TSPO expression in glioma. Methods Glioma-bearing rats were imaged with [18F]PBR06 in a microPET system. Dynamic acquisitions were acquired simultaneously upon injection of 70 - 100 MBq/0.2 mL [18F]PBR06. Over the course of scanning, arterial blood was collected to derive the input function, with HPLC radiometabolite analysis performed on selected samples for arterial input function correction. Compartmental modeling of the PET data was performed using the corrected arterial input function. Specific tumor cell binding of PBR06 was evaluated by radioligand displacement of [3H]PK 11195 with PBR06 in vitro and by displacement of [18F]PBR06 with excess PBR06 in vivo. Immediately following imaging, tumor tissue and adjacent healthy brain were harvested for assay of TSPO protein levels by western blotting and immunohistochemistry.