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A comparative study of in vitro assays for predicting the non-specific binding of PET imaging agents in vivo

Gobbi, Luca and Mercier, Joel and Bang-Andersen, Benny and Nicolas, Jean-Marie and Reilly, John and Wagner, Björn and Whitehead, David and Briard, Emmanuelle and Maguire, Ralf Paul and borroni, Edilio and Auberson, Yves (2019) A comparative study of in vitro assays for predicting the non-specific binding of PET imaging agents in vivo. ChemMedChem : chemistry enabling drug discovery, 15 (7). pp. 585-592. ISSN 1860-71791860-7187

Abstract

Abstract: Non-specific binding (NSB) is a key parameter in optimizing PET imaging tracers. We compared the ability of three available methods to predict NSB: 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.

Item Type: Article
Keywords: Imaging agents • radiopharmaceuticals • non-specific binding • positron emission tomography • fraction unbound
Date Deposited: 14 Apr 2020 00:45
Last Modified: 14 Apr 2020 00:45
URI: https://oak.novartis.com/id/eprint/41157

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