Summary: | 碩士 === 長庚大學 === 醫學影像暨放射科學系 === 100 === Background and purposes: The temporary disruption of blood-brain barrier (BBB) induced by focused ultrasound (FUS) has been proved for enhancing cerebral drug delivery and increasing non-specific uptake of ionic radiopharmaceuticals in the brain. So far, few literatures have investigated the effects of FUS-induced BBB disruption on the binding of a radiotracer specifically targeting brain receptor. The purposes of this study were to evaluate: (1) the feasibility to enhance brain uptake for [18F]AV-133, a radiopharmaceutical targeting vesicular monoamine transporter type 2 (VMAT2), upon FUS-induced BBB disruption, and (2) the effects of FUS-induced BBB disruption on the distribution of [18F]AV-133 in rat brains.
Methods: The left cerebral hemispheres of test Sprague-Dawley (SD) rats were treated with FUS. The induced BBB disruption was verified by the ex-vivo staining of intravenously injected Evans blue and by ex-vivo uptake of intravenously injected [99mTc]sodium pertechnetate in rat brains. Dynamic positron emission tomography (PET) scans were performed on the test and normal control rats after administration of [18F]AV-133 through tail veins. The uptake of [18F]AV-133 in each cerebral region was obtained and compared among brains of FUS-treated side, contralateral side, and normal control. The ex-vivo autoradiography was performed on the representative brain sections of a test rat to confirm the results of PET brain imaging.
Results: The BBB disruption in the left cerebral hemispheres of the testrats was verified by ex-vivo Evans blue staining, and also by increased ex-vivo 99mTc-sodium pertechnetate uptake as compared to the contralateral side and the normal control. The PET imaging at 85 min post-injection revealed the striatal distribution of [18F]AV-133 (%ID/c.c) in FUS-treated side (1.74) was higher than the contralateral side (1.41) and the normal control (1.57). The results of ex-vivo autoradiography also depicted a 25% higher striatal [18F]AV-133 uptake in the sections of the FUS-treated hemisphere than the contralateral side, and a 19% higher than the normal control.
Conclusions: FUS-induced BBB disruption enhanced the delivery of [18F]AV-133 to the rat brains. The increase of striatal uptake was significant. However, PET imaging also revealed some changes of [18F]AV-133 brain distribution other than the striatum in FUS-treated rats. The effect of FUS-induced BBB disruption on the specific binding of [18F]AV-133 to VMAT2 remains to be clarified. This study provided a platform for evaluating the effect of FUS treatment on specific binding between radiotracers and targets.
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