当前位置: X-MOL 学术ChemMedChem › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
A Comparative Study of in vitro Assays for Predicting the Nonspecific Binding of PET Imaging Agents in vivo.
ChemMedChem ( IF 3.4 ) Pub Date : 2019-12-04 , DOI: 10.1002/cmdc.201900608
Luca Gobbi 1 , Joël Mercier 2 , Benny Bang-Andersen 3 , Jean-Marie Nicolas 2 , John Reilly 4 , Björn Wagner 1 , David Whitehead 4 , Emmanuelle Briard 4 , R Paul Maguire 2 , Edilio Borroni 1 , Yves P Auberson 4
Affiliation  

Nonspecific binding (NSB) is a key parameter in optimizing PET imaging tracers. We compared the ability to predict NSB of three available methods: LIMBA, rat fu,brain , and CHI(IAM). Even though NSB is often associated with lipophilicity, we observed that logD does not correlate with any of these assays, clearly indicating that lipophilicity, while influencing NSB, is insufficient to predict it. A cross-comparison of the methods showed that all three correlate and are useful predictors of NSB. The three assays, however, rank the molecules slightly differently, illustrating the challenge of comparing molecules within a narrow chemical space. We also noted that CHI(IAM) values more effectively predict VNS , a measure of in vivo NSB in the human brain. CHI(IAM) measurements might be a closer model of the actual physicochemical interaction between PET tracer candidates and cell membranes, and seems to be the method of choice for the optimization of in vivo NSB.

中文翻译:

预测体内PET成像剂非特异性结合的体外分析方法的比较研究。

非特异性结合(NSB)是优化PET成像示踪剂的关键参数。我们比较了三种可用方法预测NSB的能力:LIMBA,大鼠fu,脑和CHI(IAM)。尽管NSB通常与亲脂性相关,但我们观察到logD与这些测定均不相关,这清楚地表明,亲脂性虽然会影响NSB,但不足以预测其亲脂性。方法的交叉比较表明,这三个方法均相关,并且是NSB的有用预测指标。然而,这三种测定法对分子的排名略有不同,说明了在狭窄的化学空间内比较分子的挑战。我们还注意到,CHI(IAM)值可更有效地预测VNS,VNS是人脑中体内NSB的量度。
更新日期:2019-12-13
down
wechat
bug