Positron-Emission Tomography Imaging of the TSPO with [18F]FEPPA in a Preclinical Breast Cancer Model

The present study aims to image the 18-kDa translocator protein (TSPO; formerly known as the peripheral benzodiazepine receptor) in a preclinical human breast cancer (BC) xenograft mouse model with positron-emission tomography (PET). An automated radiosynthesis of [F-18]-N-(2-(2-fluoroethoxy)benzyl)-N-(4-phenoxypyridin-3-yl)acetamide ([F-18]FEPPA) was validated for human use using a commercial synthesis module and resulted in a high radiochemical yield (30%+/- 8%, uncorrected; n = 54) and specific activity (6 +/- 4 Ci/ mu mol). Tumor uptake of [F-18]FEPPA in mice bearing subcutaneous MDA-MB-231 BC xenografts was evaluated by PET-computed tomography imaging and ex vivo biodistribution studies. Although the tumor was successfully visualized, ex vivo biodistribution studies revealed low tumor uptake (0.7%ID/g), with the majority of radioactivity distributed in the spleen, muscle, and heart despite high TSPO expression in this cell line. Our laboratory routinely prepares [F-18]FEPPA for human-imaging studies in the central nervous system, and we envision that radiopharmaceuticals that target the TSPO have the potential for imaging macrophages in the tumor microenvironment.