Journal Article [18F]FPBMP: - a potential new positron emission tomography radioligand for imaging of translocator protein (18 KDa) in peripheral organs of rat

Tiwari, Anjani  ,  Yui, Joji  ,  Zhang, Yiding  ,  Fujinaga, Masayuki  ,  Yamasaki, Tomoteru  ,  Xie, Lin  ,  Shimoda, Yoko  ,  Kumata, Katsushi  ,  Hatori, Akiko  ,  Ming-Rong, Zhang

5 ( 123 )  , pp.101447 - 101454 , 2015-12
The five transmembrane translocator protein (18 kDa, TSPO) is abundantly expressed in the mitochondria of activated microglia (brain) and peripheral tissues, including those of the heart, lung and kidney. We recently developed the 18F-labelled molecule 2-[5-(4-[18F]fluoropropyloxyphenyl)-2-oxo-1,3-benzoxazol-3(2H)-yl]-N-methyl-N-phenylacetamide ([18F]FPBMP) as a novel positron emission tomography (PET) radioligand for imaging TSPO. In this study, we have evaluated the pharmacokinetics of this radioligand based on its biodistribution in mice, as well as the results of PET and metabolite studies in rats. The specificity of [18F]FPBMP towards TSPO was assessed by blocking experiments involving the intravenous injection of 1 mg kg−1 of unlabeled PK11195. A metabolite study was performed in the plasma and peripheral organs of rats by HPLC methods. The ex vivo biodistribution of [18F]FPBMP in mice showed a high uptake of radioactivity in TSPO enriched peripheral organs, especially in the lung, heart and kidney. The in vivo biodistribution of this compound was evaluated through PET summation images of rats 1–10, 10–20, 20–30 and 50–60 min after the injection of the radioligand. The TSPO-enriched organs, including the heart, kidney and lung, were clearly visualized. Pre-treatment with TSPO-specific PK11195 minimized the uptake of [18F]FPBMP in the TSPO-enriched tissues, thereby confirming its selectivity for TSPO. Metabolite analysis in rats confirmed the presence of [18F]FPBMP in the heart, lung and kidney up to 60 min. In summary, these data demonstrate that [18F]FPBMP is a suitable PET ligand for the imaging of TSPO in peripheral tissues.

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