Development of a novel radioligand for imaging 18-kD translocator protein (TSPO) in a rat model of Parkinson’s disease

Chun-Yi Wu; Yang-Yi Chen; Jia-Jia Lin; Jui-Ping Li; Jen-Kun Chen; Te-Chun Hsieh; Chia-Hung Kao

doi:10.1186/s12880-019-0375-8

BMC Medical Imaging (Sep 2019)

Development of a novel radioligand for imaging 18-kD translocator protein (TSPO) in a rat model of Parkinson’s disease

Chun-Yi Wu,
Yang-Yi Chen,
Jia-Jia Lin,
Jui-Ping Li,
Jen-Kun Chen,
Te-Chun Hsieh,
Chia-Hung Kao

Affiliations

Chun-Yi Wu: Department of Biomedical Imaging and Radiological Science, China Medical University
Yang-Yi Chen: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University
Jia-Jia Lin: Department of Biomedical Imaging and Radiological Science, China Medical University
Jui-Ping Li: Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes
Jen-Kun Chen: Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes
Te-Chun Hsieh: Department of Biomedical Imaging and Radiological Science, China Medical University
Chia-Hung Kao: Graduate Institute of Biomedical Sciences and School of Medicine, College of Medicine, China Medical University

DOI: https://doi.org/10.1186/s12880-019-0375-8
Journal volume & issue: Vol. 19, no. 1
pp. 1 – 9

Abstract

Read online

Abstract Purpose The inflammation reaction in the brain may stimulate damage repair or possibly lead to secondary brain injury. It is often associated with activated microglia, which would overexpress 18-kDa translocator protein (TSPO). In this study, we successfully developed a new TSPO radioligand, [18F]-2-(4-fluoro-2-(p-tolyloxy)phenyl)-1,2-dihydroisoquinolin-3(4H)-one ([18F]FTPQ), and evaluate its potential to noninvasively detect brain changes in a rat model of Parkinson’s disease (PD). Procedures The precursor (8) for [18F]FTPQ preparation was synthesized via six steps. Radiofluorination was carried out in the presence of a copper catalyst, and the crude product was purified by high-performance liquid chromatography (HPLC) to give the desired [18F]FTPQ. The rat model of PD was established by the injection of 6-OHDA into the right hemisphere of male 8-week-old Sprague-Dawley rats. MicroPET/CT imaging and immunohistochemistry (IHC) were performed to characterize the biological properties of [18F]FTPQ. Results The overall chemical yield for the precursor (8) was around 14% after multi-step synthesis. The radiofluorination efficiency of [18F]FTPQ was 60 ± 5%. After HPLC purification, the radiochemical purity was higher than 98%. The overall radiochemical yield was approximately 19%. The microPET/CT images demonstrated apparent striatum accumulation in the brains of PD rats at the first 30 min after intravenous injection of [18F]FTPQ. Besides, longitudinal imaging found the uptake of [18F]FTPQ in the brain may reflect the severity of PD. The radioactivity accumulated in the ipsilateral hemisphere of PD rats at 1, 2, and 3 weeks after 6-OHDA administration was 1.84 ± 0.26, 3.43 ± 0.45, and 5.58 ± 0.72%ID/mL, respectively. IHC revealed that an accumulation of microglia/macrophages and astrocytes in the 6-OHDA-injected hemisphere. Conclusions In this study, we have successfully synthesized [18F]FTPQ with acceptable radiochemical yield and demonstrated the feasibility of [18F]FTPQ as a TSPO radioligand for the noninvasive monitoring the disease progression of PD.

Published in BMC Medical Imaging

ISSN: 1471-2342 (Online)
Publisher: BMC
Country of publisher: United Kingdom
LCC subjects: Medicine: Medicine (General): Medical technology
Website: http://bmcmedimaging.biomedcentral.com

About the journal

Abstract

Keywords