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Abstract

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 TSPOradiotracers, [18F]fluoromethyl-PBR28 ([18F]1) and [18F]CB251 ([18F]2). 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. [18F]2 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 [18F]1 did not show a significant difference between the two groups. Histopathological characterization revealed that a prominent positron emission tomography (PET) signal of [18F]2 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 [18F]2 is a sensitive tool for noninvasively diagnosing myocarditis related to inflammation of the heart muscle by assessing abnormal TSPO expression.

Author information

Kim GR1,2, Paeng JC3, Jung JH4, Moon BS5, Lopalco A6, Denora N7, Lee BC8,9, Kim SE10,11,12.

1 Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Korea. kgram@snu.ac.kr.
2 Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 16229, Korea. kgram@snu.ac.kr.
3 Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Seoul 03080, Korea. paengjc@paran.com.
4 Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Korea. jaehoboa@paran.com.
5 Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Korea. bsmoon@snu.ac.kr.
6 Department of Pharmacy-Drug Sciences, University of Bari "Aldo Moro", Bari 70125, Italy. antonio.lopalco@uniba.it.
7 Department of Pharmacy-Drug Sciences, University of Bari "Aldo Moro", Bari 70125, Italy. nunzio.denora@uniba.it.
8 Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Korea. leebc@snu.ac.kr.
9 Center for Nanomolecular Imaging and Innovative Drug Development, Advanced Institutes of Convergence Technology, Suwon 16229, Korea. leebc@snu.ac.kr.
10 Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam 13620, Korea. kse@snu.ac.kr.
11 Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 16229, Korea. kse@snu.ac.kr.
12 Center for Nanomolecular Imaging and Innovative Drug Development, Advanced Institutes of Convergence Technology, Suwon 16229, Korea. kse@snu.ac.kr.