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Review
. 2022 Apr;111(4):774-785.
doi: 10.1002/cpt.2548. Epub 2022 Feb 24.

PET as a Translational Tool in Drug Development for Neuroscience Compounds

Andrea Varrone  1 , Christoffer Bundgaard  2 , Benny Bang-Andersen  1   3
Affiliations
Review

PET as a Translational Tool in Drug Development for Neuroscience Compounds

Andrea Varrone et al. Clin Pharmacol Ther. 2022 Apr.

Abstract

In central nervous system drug discovery programs, early development of new chemical entities (NCEs) requires a multidisciplinary strategy and a translational approach to obtain proof of distribution, proof of occupancy, and proof of function in specific brain circuits. Positron emission tomography (PET) provides a way to assess in vivo the brain distribution of NCEs and their binding to the target of interest, provided that radiolabeling of the NCE is possible or that a suitable radioligand is available. PET is therefore a key tool for early phases of drug discovery programs. This review will summarize the main applications of PET in early drug development and discuss the usefulness of PET microdosing studies performed with direct labelling of the NCE and PET occupancy studies. The purpose of this review is also to propose an alignment of the nomenclatures used by drug metabolism and pharmacokinetic scientists and PET imaging scientists to indicate key pharmacokinetic parameters and to provide guidance in the performance and interpretation of PET studies.

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Conflict of interest statement

A.V., C.B., and B.B.‐A. are employed at H. Lundbeck A/S.

Figures

Figure 1
Figure 1
Positron emission tomography (PET) can be applied for different purposes, in relation to the characterization of the drug or to the study of different aspects of the disease. This review will focus on the methods/endpoints highlighted in the right‐hand side of the circle.
Figure 2
Figure 2
Rigorous preclinical characterization and alignment of biodistribution technologies before moving into the clinic with confidence using positron emission tomography (PET) microdosing.
Figure 3
Figure 3
Suggested flowchart for the assessment of the pharmacokinetic properties of radiolabeled central nervous system (CNS) drugs using the microdosing approach. PET, positron emission tomography.
See this image and copyright information in PMC

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