[18F]BIBD-239: 18F-Labeled ER176, a Positron Emission Tomography Tracer Specific for the Translocator Protein

• DOI: 10.1021/acs.molpharmaceut.2c00157
• Publication Date: 2022-06-07T17:23:22Z
• Authors: Hualong Chen; Zeng Jiang; Xuebo Cheng; Wei Zheng; Yuli Sun; Ziyue Yu; Tingyu Yang; Lu Zhang; Jun Yan; Yajing Liu; Xunming Ji; Zehui Wu
• Keywords: Translocator protein; Radioligand

[11C]ER176 has adequate sensitivity to image the human brain translocator protein (TSPO) in all three genotypes by positron emission tomography (PET). However, its clinical application is limited short half-life of 11C (20.38 min). To overcome deficiency and keep pharmacophore features ER176 maximum extent, we designed four fluorine-labeled derivatives using deuterium method. In vitro competition binding confirmed that compounds had high affinity for TSPO. Biodistribution experiments showed tissues with expression TSPO uptake these compounds, as well compound penetration mild defluorination vivo. Therefore, [18F]BIBD-239 simple synthesis conditions was selected further biological evaluation. Theoretical simulations BIBD-239 have similar modes sites Ala147-TSPO Thr147-TSPO, which indicated tracers may consistent genotypes. autoradiography vivo PET studies ischemic rat dramatically higher on lesion site compared contralateral side good kinetics. Additionally, provided clear tumor images a GL261 glioma model. Importantly, imaging liquid chromatography–high-resolution mass spectrometry (LC-HRMS) results other metabolites did not interfere imaging. Conclusively, [18F]BIBD-239, low polymorphism sensitivity, labeling conditions, yield, affinity, specificity TSPO, it planned evaluation species.