Watanabe Hiroyuki, Tarumizu Yuta, Kaide Sho, Shimizu Yoichi, Iikuni Shimpei, Nakamoto Yuji, Ono Masahiro
Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
Department of Diagnostic Imaging and Nuclear Medicine, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan.
ACS Med Chem Lett. 2021 Jan 11;12(2):262-266. doi: 10.1021/acsmedchemlett.0c00641. eCollection 2021 Feb 11.
Noninvasive imaging of tau aggregates with a positron emission tomography (PET) tracer is useful for the diagnosis and staging of Alzheimer's disease (AD). Recently, we found that benzimidazopyridine (BIP) is an attractive scaffold for developing PET and single photon computed emission tomography tracers targeting tau aggregates. In this study, we designed and synthesized five novel F-labeled compounds with various substituted groups or atoms at the 7-position of the BIP scaffold. In autoradiographic studies, all F-labeled BIP derivatives selectively bound to tau aggregates deposited in AD brain sections. On the other hand, the initial brain uptake of these compounds was affected by the type of substituted group or halogen atom introduced into the 7-position of the BIP scaffold. Among these compounds, [F]Me-BIPF showed the highest brain uptake (6.79% ID/g at 2 min postinjection) and 2 min/60 min ratio (3.59). These results suggest that appropriate introduction of the substituted group or atom into the 7-position of the BIP scaffold may be effective for developing useful tau PET tracers.
使用正电子发射断层扫描（PET）示踪剂对tau蛋白聚集体进行无创成像，对阿尔茨海默病（AD）的诊断和分期很有用。最近，我们发现苯并咪唑并吡啶（BIP）是开发靶向tau蛋白聚集体的PET和单光子计算机发射断层扫描示踪剂的一个有吸引力的骨架。在本研究中，我们设计并合成了五种新型的F标记化合物，它们在BIP骨架的7位带有各种取代基或原子。在放射自显影研究中，所有F标记的BIP衍生物都选择性地结合到沉积在AD脑切片中的tau蛋白聚集体上。另一方面，这些化合物的初始脑摄取受引入到BIP骨架7位的取代基或卤原子类型的影响。在这些化合物中，[F]Me - BIPF显示出最高的脑摄取（注射后2分钟时为6.79% ID/g）和2分钟/60分钟比值（3.59）。这些结果表明，在BIP骨架的7位适当引入取代基或原子可能对开发有用的tau PET示踪剂有效。
