Arakawa Ryosuke, Okumura Masaki, Ito Hiroshi, Seki Chie, Takahashi Hidehiko, Takano Harumasa, Nakao Ryuji, Suzuki Kazutoshi, Okubo Yoshiro, Halldin Christer, Suhara Tetsuya
Molecular Neuroimaging Group, Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, Japan.
J Nucl Med. 2008 Aug;49(8):1270-6. doi: 10.2967/jnumed.108.051292. Epub 2008 Jul 16.
(S,S)-18F-FMeNER-D2 was recently developed as a radioligand for the measurement of norepinephrine transporter imaging with PET. In this study, a norepinephrine transporter was visualized in the human brain using this radioligand with PET and quantified by several methods.
PET scans were performed on 10 healthy men after intravenous injection of (S,S)-18F-FMeNER-D2. Binding potential relative to nondisplaceable binding (BP(ND)) was quantified by the indirect kinetic, simplified reference-tissue model (SRTM), multilinear reference-tissue model (MRTM), and ratio methods. The indirect kinetic method was used as the gold standard and was compared with the SRTM method with scan times of 240 and 180 min, the MRTM method with a scan time of 240 min, and the ratio method with a time integration interval of 120-180 min. The caudate was used as reference brain region.
Regional radioactivity was highest in the thalamus and lowest in the caudate during PET scanning. BP(ND) values by the indirect kinetic method were 0.54 +/- 0.19 and 0.35 +/- 0.25 in the thalamus and locus coeruleus, respectively. BP(ND) values found by the SRTM, MRTM, and ratio methods agreed with the values demonstrated by the indirect kinetic method (r = 0.81-0.92).
The regional distribution of (S,S)-18F-FMeNER-D2 in our study agreed with that demonstrated by previous PET and postmortem studies of norepinephrine transporter in the human brain. The ratio method with a time integration interval of 120-180 min will be useful for clinical research of psychiatric disorders for estimation of norepinephrine transporter occupancy by antidepressants without requiring arterial blood sampling and dynamic PET.
（S,S）-18F-FMeNER-D2最近被开发作为一种放射性配体，用于正电子发射断层扫描（PET）测量去甲肾上腺素转运体成像。在本研究中，使用这种放射性配体和PET在人脑内可视化去甲肾上腺素转运体，并通过几种方法进行定量分析。
对10名健康男性静脉注射（S,S）-18F-FMeNER-D2后进行PET扫描。相对于不可置换结合的结合潜能（BP(ND)）通过间接动力学、简化参考组织模型（SRTM）、多线性参考组织模型（MRTM）和比值法进行定量分析。间接动力学方法作为金标准，与扫描时间为240分钟和180分钟的SRTM方法、扫描时间为240分钟的MRTM方法以及时间积分间隔为120 - 180分钟的比值法进行比较。尾状核用作参考脑区。
PET扫描期间，丘脑的区域放射性最高，尾状核最低。间接动力学方法测得的丘脑和蓝斑核的BP(ND)值分别为0.54±0.19和0.35±0.25。SRTM、MRTM和比值法测得的BP(ND)值与间接动力学方法测得的值一致（r = 0.81 - 0.92）。
本研究中（S,S）-18F-FMeNER-D2的区域分布与先前关于人脑去甲肾上腺素转运体的PET和尸检研究结果一致。时间积分间隔为120 - 180分钟的比值法将有助于精神疾病的临床研究，用于估计抗抑郁药对去甲肾上腺素转运体的占有率，而无需动脉血采样和动态PET检查。
