Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Korea.
Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 16229, Korea.
Int J Mol Sci. 2018 Jan 17;19(1):276. doi: 10.3390/ijms19010276.
Overexpression of the 18-kDa translocator protein (TSPO) is closely linked to inflammatory responses in the heart, including myocarditis, which can lead to myocardial necrosis. In vivo assessment of inflammatory responses has enabled the precise diagnosis of myocarditis to improve clinical outcomes. Here, we evaluated TSPO overexpression in a rat model of experimental autoimmune myocarditis (EAM) compared to healthy rats using two TSPO radiotracers, [F]fluoromethyl-PBR28 ([F]) and [F]CB251 ([F]). All radiolabeling methods were successfully applied to an automated module for the reproducible preparation of TSPO radiotracers. Both radiotracers were directly compared in an EAM rat model, as well as in healthy rats to determine whether either radiotracer provides a more promising assessment of in vivo TSPO overexpression. [F] provided more specific TSPO-uptake in the heart of the EAM rats (1.32-fold that of the heart-to-lung uptake ratio versus healthy controls), while [F] did not show a significant difference between the two groups. Histopathological characterization revealed that a prominent positron emission tomography (PET) signal of [F] in the EAM rats corresponded to the presence of a higher density of TSPO compared to the healthy controls. These results suggest that the imidazole[1,2-a]pyridine-based radiotracer [F] is a sensitive tool for noninvasively diagnosing myocarditis related to inflammation of the heart muscle by assessing abnormal TSPO expression.
TSPO 的过度表达与心脏的炎症反应密切相关，包括心肌炎，可导致心肌坏死。对炎症反应的体内评估使心肌炎的精确诊断得以实现，从而改善了临床结果。在这里，我们使用两种 TSPO 放射性示踪剂 [F]氟甲基-PBR28([F])和 [F]CB251([F])，评估了实验性自身免疫性心肌炎(EAM)大鼠模型中 TSPO 的过度表达与健康大鼠相比。所有放射性标记方法均成功应用于自动化模块，以可重复的方式制备 TSPO 放射性示踪剂。我们在 EAM 大鼠模型以及健康大鼠中直接比较了这两种放射性示踪剂，以确定哪种放射性示踪剂更能有前途地评估体内 TSPO 的过度表达。[F]在 EAM 大鼠的心脏中提供了更特异性的 TSPO 摄取（与健康对照组相比，心脏与肺摄取比值增加了 1.32 倍），而 [F]在两组之间没有显示出显著差异。组织病理学特征表明，EAM 大鼠中 [F]的正电子发射断层扫描（PET）信号明显，与 TSPO 的密度高于健康对照组相对应。这些结果表明，基于咪唑[1,2-a]吡啶的放射性示踪剂 [F]是一种敏感的工具，可通过评估异常的 TSPO 表达来非侵入性诊断与心肌炎症相关的心肌炎。
