國家衛生研究院 NHRI:Item 3990099045/12197
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    题名: Development of a novel radioligand for imaging 18-kD translocator protein (TSPO) in a rat model of Parkinson's disease
    作者: Wu, CY;Chen, YY;Lin, JJ;Li, JP;Chen, JK;Hsieh, TC;Kao, CH
    贡献者: Institute of Biomedical Engineering and Nanomedicine
    摘要: 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, [F-18]-2-(4-fluoro-2-(p-tolyloxy)phenyl)-1,2-dihydroisoquinolin-3(4H)-one ([F-18]FTPQ), and evaluate its potential to noninvasively detect brain changes in a rat model of Parkinson's disease (PD). Procedures The precursor (8) for [F-18]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 [F-18]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 [F-18]FTPQ. Results The overall chemical yield for the precursor (8) was around 14% after multi-step synthesis. The radiofluorination efficiency of [F-18]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 [F-18]FTPQ. Besides, longitudinal imaging found the uptake of [F-18]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 [F-18]FTPQ with acceptable radiochemical yield and demonstrated the feasibility of [F-18]FTPQ as a TSPO radioligand for the noninvasive monitoring the disease progression of PD.
    日期: 2019-09
    關聯: BMC Medical Imaging. 2019 Sep;19:Article number 78.
    Link to: http://dx.doi.org/10.1186/s12880-019-0375-8
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1471-2342&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000486722100001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85072403232
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