11C-DPA-713 has much greater specific binding to translocator protein 18 kDa (TSPO) in human brain than 11C-(R)-PK11195
11C-DPA-713 has much greater specific binding to translocator protein 18 kDa (TSPO) in human brain than 11C-(R)-PK11195
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DOI：
10.1177/0271678x17699223
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发表时间：
2018-03-01
影响因子：
6.3
通讯作者：
Fujita, Masahiro
中科院分区：
文献类型：
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作者：
Kobayashi, Masato;Jiang, Teresa;Fujita, Masahiro
易位蛋白 18 kDa (TSPO) 的正电子发射断层扫描 (PET) 放射性配体广泛用于测量神经炎症，但第二代放射性配体在人体成像中是否优于原型剂 C-11-(R)-PK11195 存在争议。本研究试图定量测量 C-11-(R)-PK11195 与最有前途的第二代放射性配体之一 C-11-(R)-PK11195 的“信号与背景”比（评估为结合电位 (BPND)）。健康受试者在注射 C-11-(R)-PK11195 后进行动态 PET 扫描和动脉血测量。 （16 名受试者）或 C-11-DPA-713（22 名受试者），在服用 TSPO 阻断药物 XBD173（30-90 mg PO）后对这些受试者的子集进行了扫描，C-11-(R)-PK11195 显示出对大脑中基因型的显着敏感性，而 C-11-(R)-PK11195 则没有。尽管 C-11-DPA-713 的高特异性结合表明，C-11-DPA-713 的特异性结合远高于 C-11-(R)-PK11195，但 C-11-DPA-713 (7.3) 的 BPND 大约高 10 倍。是测量 TSPO 的理想配体，我们还发现其分布体积随着时间的推移而增加，与大脑中放射性代谢物的积累一致。
Positron emission tomography (PET) radioligands for translocator protein 18 kDa (TSPO) are widely used to measure neuroinflammation, but controversy exists whether second-generation radioligands are superior to the prototypical agent C-11-(R)-PK11195 in human imaging. This study sought to quantitatively measure the "signal to background'' ratio (assessed as binding potential (BPND)) of C-11-(R)-PK11195 compared to one of the most promising second-generation radioligands, C-11-(R)-PK11195 . Healthy subjects had dynamic PET scans and arterial blood measurements of radioligand after injection of either C-11-(R)-PK11195 (16 subjects) or C-11-DPA-713 (22 subjects). To measure the amount of specific binding, a subset of these subjects was scanned after administration of the TSPO blocking drug XBD173 (30-90 mg PO). C-11-(R)-PK11195 showed a significant sensitivity to genotype in brain, whereas C-11-(R)-PK11195did not. Lassen occupancy plot analysis revealed that the specific binding of C-11-DPA-713 was much greater than that of C-11-(R)-PK11195. The BPND in high-affinity binders was about 10-fold higher for C-11-DPA-713 (7.3) than for C-11-(R)-PK11195 (0.75). Although the high specific binding of C-11-DPA-713 suggests it is an ideal ligand to measure TSPO, we also found that its distribution volume increased over time, consistent with the accumulation of radiometabolites in brain.