会議発表用資料 Quantitative PET for monitoring blood–brain barrier opening induced by focused ultrasound by 2-amino-[3-11C]isobutyric acid

Okada, Maki  ,  Kikuchi, Tatsuya  ,  Okamura, Toshimitsu  ,  Tsuji, Atsushi  ,  Wakizaka, Hidekatsu  ,  Ming-Rong, Zhang  ,  Kato, Koichi

2015-11-09
内容記述
Objectives: The blood-brain barrier (BBB) plays an important role in protecting the central nervous system by restricting the entry of substances, and it also prevents the transport of therapeutic agencies. Several BBB-opening operation methods have been developed to improve the chemotherapeutic efficacy of cerebral diseases such as brain tumors. It is needed to monitor the BBB condition noninvasively, high sensitively and quantitatively and repeatedly to optimize the BBB-opening operation for effective chemotherapeutic strategies. We recently developed an efficient method for preparing 11C-labeled 2-aminoisobutyric acid AIB ([3-11C]AIB) 1), and we also reported that in vivo [3-11C]AIB PET in rats opened BBB by focused ultrasound (FUS) and microbubbles visualized BBB-opened region 2). In the present study, we evaluated the effect of FUS intensity on BBB permeability by in vivo [3-11C]AIB PET.Results and Discussion: The PET studies of [3-11C]AIB in rats were conducted at 5 min after operation of BBB by 1-MHz FUS (0.33 and 0.49 MPa) with microbubbles. The uptake of [3-11C]AIB in both 0.33- and 0.49-MPa-FUS-sonicated sides were significantly higher than that in each contralateral side and increased with time. The 0.49-MPa-FUS sonication resulted in higher uptake of [3-11C]AIB than the 0.33-MPa-FUS sonication. The blood-to–brain influx rate constants (Ki) values were estimated from Patlak plots with the data of arterial plasma analysis and PET. The arterial plasma [3-11C]AIB radioactivity rapidly decreased by 10 min, and then approximately 0.5% of injected dose per mL of radioactivity remained from 20 min to 60 min 2). The Ki values of FUS-sonicated sides were significantly higher (4.1 and 7.3 μL/g/min at 0.33 and 0.49 MPa, respectively) than those of the corresponding contralateral sides (1.7 and 1.8 μL/g/min at 0.33 and 0.49 MPa, respectively). The BBB permeability status is affected by various FUS and microbubble condition such as FUS intensity, sonication duration, and concentration of microbubbles and moreover, these effects of FUS also differ among patients. Therefore, quantitative Ki value obtained by [3-11C]AIB PET could be a useful indicator for optimizing the BBB-opening operation by FUS.Conclusions: [3-11C]AIB PET visualized the BBB-opened area noninvasively, high sensitively and quantitatively and could determine the quantitative Ki value as an indicator of BBB permeability. Therefore, PET imaging with [3-11C]AIB is a promising method for quantitative BBB permeability measurements.
Ninth Japan-China Joint Seminar on Radiopharmaceutical Chemistry

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