Development of a novel radioligand for imaging 18-kD translocator protein (TSPO) in a rat model of Parkinson's disease.
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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.
SUBMITTER: Wu CY
PROVIDER: S-EPMC6751751 | biostudies-literature | 2019 Sep
REPOSITORIES: biostudies-literature
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