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Rapid screening of nine unradiolabeled candidate compounds as PET brain imaging agents using cassette-wave microdosing and LC-MS/MS.

The R&D of PET imaging agents is a complex system engineering, simplifying screening steps and increasing screening efficiency have become popular issues. The purpose of this study is to develop a new screening procedure using cassette-wave microdosing and LC-MS/MS to enhance the screening throughput of unradiolabeled candidate compounds as PET imaging agents. Nine compounds were divided into 3 sets and made into 3 cassettes. Fifteen rats were randomly divided into 3 groups, and every animal received three intravenous bolus injections at three different time points; the doses were at microdose levels. This dosing approach takes advantage of temporal and spatial differences and is likened to an input wave; therefore, this approach was named cassette-wave microdosing. The samples of different brain regions such as the hypothalamus, striatum, hippocampus, cortex, cerebellum and the remainder of the brain were detected by LC-MS/MS analysis. The research potential of the compounds as PET imaging agents is evaluated in terms of brain biodistribution data. The screening method is rapid, highly efficient, reliable and reduces animal usage. Additionally, it can shorten the evaluation process of radiopharmaceuticals and enhance the screening throughput of PET radiopharmaceuticals without the use of radioactive agents.

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