Ming Ni, Xingxing Zhu, Kaixuan Wang, Wenliang Guo, Qin Shi, Yuying Li, Mengchao Cui* and Qiang Xie*, 

摘要

[18F]-4-((E)-((E)-4-(2-(2-(2-氟乙氧基)乙氧基)乙氧基)亞芐基)-肼基)甲基)-N-甲基苯胺（[18F]92）是一種新型正電子發(fā)射斷層掃描（PET）示蹤劑，以前曾報(bào)道過(guò)它與聚集的β淀粉樣蛋白（Aβ）具有很高的結(jié)合親和力。本研究旨在報(bào)告[18F]92的全自動(dòng)放射合成過(guò)程，探索其在健康受試者大腦中的放射性分布，并研究其在阿爾茨海默?。ˋD）早期診斷中的潛在應(yīng)用價(jià)值。[18F]92的全自動(dòng)放射合成是在AllinOne模塊上完成的。這項(xiàng)研究招募了 31 名參與者。在 0-90 分鐘內(nèi)進(jìn)行動(dòng)態(tài)[18F]92 PET 成像，以評(píng)估認(rèn)知正常（CN）受試者的時(shí)間-活動(dòng)曲線（TAC）和標(biāo)準(zhǔn)化攝取值比（SUVR）曲線。所有參與者均被目測(cè)分為陽(yáng)性（+）或陰性（-）。通過(guò)計(jì)算不同相關(guān)區(qū)域的 SUVR，對(duì)[18F]92 進(jìn)行了半定量分析。此外，研究還分析了全局 SUVR 與血漿 AD 生物標(biāo)志物（包括 Aβ42、Aβ40、P-tau181 和 T-tau）之間的關(guān)系。[18F]92的自動(dòng)放射合成在50分鐘內(nèi)完成，放射化學(xué)純度超過(guò)95%，放射化學(xué)產(chǎn)率為36±3%（非衰變校正）。參與者中，15 人估計(jì)為 Aβ (-)，16 人估計(jì)為 Aβ (+)。TAC顯示，[18F]92在10分鐘內(nèi)迅速穿過(guò)血腦屏障，隨后迅速下降，在最后50-90分鐘內(nèi)下降速度減慢。SUVR曲線顯示，SUVR值在注射后60-70分鐘左右趨于穩(wěn)定，在70-90分鐘之間達(dá)到平衡，主要集中在大腦皮層。在大腦皮層內(nèi)，Aβ (+) 參與者的 SUVR 明顯高于 Aβ (-) 參與者。此外，Aβ42和Aβ42/Aβ40比值與總體SUVR呈負(fù)相關(guān)，而血漿P-tau181和P-tau181/T-tau比值與總體SUVR呈正相關(guān)。[18F]92在人腦中表現(xiàn)出良好的藥代動(dòng)力學(xué)特性，并且可以大規(guī)模自動(dòng)合成。[18F]92是一種很有前景且可靠的放射性示蹤劑，可用于估計(jì)Aβ的病理積累，為AD診斷和治療藥物的臨床試驗(yàn)提供有價(jià)值的幫助。

本文章由計(jì)算機(jī)程序翻譯，如有差異，請(qǐng)以英文原文為準(zhǔn)。

Novel β-amyloid PET Imaging Study of [18F]92 in Patients with Cognitive Decline

[18F]-4-((E)-(((E)-4-(2-(2-(2-Fluoroethoxy)ethoxy)ethoxy)benzylidene)-hydrazono)methyl)-N-methylaniline ([18F]92) is a novel positron emission tomography (PET) tracer previously reported to exhibit high binding affinity to aggregated β-amyloid (Aβ). This study aims to report a fully automated radiosynthesis procedure for [18F]92, explore its radioactive distribution in the brains of healthy subjects, and investigate its potential application value in the early diagnosis of Alzheimer’s disease (AD). The fully automated radiosynthesis of [18F]92 was performed on the AllinOne module. Thirty one participants were recruited for this study. Dynamic [18F]92 PET imaging was conducted over 0–90 min period to assess time–activity curves (TAC) and standardized uptake value ratio (SUVR) curves in cognitively normal (CN) subjects. All participants were visually classified as either positive (+) or negative (?). Semiquantitative analyses of [18F]92 were performed by calculating SUVRs in different regions of interest. Furthermore, the study analyzed the relationships between global SUVR and plasma AD biomarkers, including Aβ42, Aβ40, P-tau181, and T-tau. The automated radiosynthesis of [18F]92 was completed within 50 min, yielding a radiochemical purity of greater than 95% and a radiochemical yield of 36 ± 3% (nondecay-corrected). Among the participants, 15 were estimated as Aβ (?) and 16 as Aβ (+). TACs indicated that [18F]92 rapidly crossed the blood–brain barrier within 10 min, followed by a rapid decrease, which then slowed down in the last 50–90 min. SUVR curves revealed that SUVR values stabilized around 60–70 min after injection and reached an equilibrium between 70 and 90 min, primarily in the cerebral cortex. SUVRs of Aβ (+) participants were significantly higher than those of Aβ (?) individuals within the cerebral cortex. In addition, Aβ42 and the Aβ42/Aβ40 ratio exhibited negative correlations with global SUVR, while plasma P-tau181 and the P-tau181/T-tau ratio displayed positive correlations with global SUVR. [18F]92 exhibits excellent pharmacokinetic properties in the human brain and can be synthesized automatically on a large scale. [18F]92 is a promising and reliable radiotracer for estimating Aβ pathology accumulation, providing valuable assistance in AD diagnosis and guiding clinical trials of therapeutic drugs.

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網(wǎng)址: 認(rèn)知功能減退患者的新型[18F]92 β 淀粉樣蛋白 PET 成像研究 http://www.u1s5d6.cn/newsview540761.html