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BMC Medical Imaging
Published in: BMC Medical Imaging 1/2019

Open Access 01-12-2019 | Positron Emission Tomography | Research article

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

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

Published in: BMC Medical Imaging | Issue 1/2019

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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.
Appendix
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Metadata
Title
Development of a novel radioligand for imaging 18-kD translocator protein (TSPO) in a rat model of Parkinson’s disease
Authors
Chun-Yi Wu
Yang-Yi Chen
Jia-Jia Lin
Jui-Ping Li
Jen-Kun Chen
Te-Chun Hsieh
Chia-Hung Kao
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Medical Imaging / Issue 1/2019
Electronic ISSN: 1471-2342
DOI
https://doi.org/10.1186/s12880-019-0375-8

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