PDF(Pubmed)
Abstract：
Non-invasive imaging of GSK-3 expression in the brain will help to understand the role of GSK-3 in disease pathology and progression. Herein, we report the radiosynthesis and evaluation of two novel isonicotinamide based 18F labeled PET probes, [18F]2 and [18F]6 for noninvasive imaging of GSK3. Among the developed PET probes, the in vitro blood-brain permeability coefficient of 2 (38 ± 20 × 10-6 cm/s, n = 3) was found to be better than 6 (8.75 ± 3.90 × 10-6 cm/s, n = 5). The reference compounds 2 and 6 showed nanomolar affinity towards GSK-3α and GSK-3β. PET probe [18F]2 showed higher stability (100%) in mouse and human serums compared to [18F]6 (67.01 ± 4.93%, n = 3) in mouse serum and 66.20 ± 6.38%, n = 3) in human serum at 120 min post incubation. The in vivo imaging and blocking studies were performed in wild-type mice only with [18F]2 due to its observed stability. [18F]2 showed a SUV of 0.92 ± 0.28 (n = 6) in mice brain as early as 5 min post-injection followed by gradual clearance over time.
摘要：
脑中GSK-3表达的非侵入性成像将有助于了解GSK-3在疾病病理和进展中的作用。在这里，我们报道了两种新的基于异烟酰胺的18F标记的PET探针的放射合成和评估，[18F]2和[18F]6用于GSK3的非侵入性成像。在开发的PET探针中，体外血脑通透性系数为2（38±20×10-6cm/s，n=3)优于6(8.75±3.90×10-6cm/s,n=5)。参考化合物2和6显示出对GSK-3α和GSK-3β的纳摩尔亲和力。与[18F]6相比，PET探针[18F]2在小鼠和人血清中显示出更高的稳定性（100％）（67.01±4.93％，n=3）在小鼠血清中和66.20±6.38％，n=3)在培养后120分钟的人血清中。由于观察到的稳定性,在仅具有[18F]2的野生型小鼠中进行体内成像和阻断研究。[18F]2显示小鼠脑中早在注射后5分钟的SUV为0.92±0.28(n=6),随后随时间逐渐清除。
