Positron Emission Tomography in CNS Drug Discovery and Drug Monitoring

Abstract

Molecular imaging methods such as positron emission tomography (PET) are increasingly involved in the development of new drugs. Using radioactive tracers as imaging probes, PET allows the determination of the pharmacokinetic and pharmacodynamic properties of a drug candidate, via recording target engagement, the pattern of distribution, and metabolism. Because of the noninvasive nature and quantitative end point obtainable by molecular imaging, it seems inherently suited for the examination of a pharmaceutical's behavior in the brain. Molecular imaging, most especially PET, can therefore be a valuable tool in CNS drug research. In this Perspective, we present the basic principles of PET, the importance of appropriate tracer selection, the impact of improved radiopharmaceutical chemistry in radiotracer development, and the different roles that PET can fulfill in CNS drug research.

Considerations in the Development of Reversibly Binding PET Radioligands for Brain Imaging

“…Moreover, the interactions of drugs or experimental therapeutics with brain proteins may be assessed. Therefore, these molecular imaging techniques have become integral to CNS drug discovery and development programs [5–8], and are also important for monitoring the neurochemical effects of drug treatments or therapies [8]. …”

A Novel Potential Positron Emission Tomography Imaging Agent for Vesicular Monoamine Transporter Type 2

“…PET tracers designed to target specific neurochemical processes offer new possibilities for improving the differentiation of various central nervous system-related disorders, such as dementia [2]. Therefore, because of the physiological importance of VMAT2, we proposed to synthesize 10-(+)- 11 C-DTBZ, the regioisomer of 9-(+)- 11 C-DTBZ, which has been widely used for VMAT2 imaging, and we performed a comparative in vivo evaluation of both radiotracers.…”

“…Vesicular monoamine transporter 2 (VMAT2), a member of the solute carrier family 18 with 12 transmembrane domains, is the protein responsible for transporting monoamine neurotransmitters (dopamine, norepinephrine, serotonin) into synaptic vesicles for subsequent storage and release [1,2]. VMAT2 abnormalities have been implicated in a variety of neurodegenerative disorders, including Parkinson’s and Huntington’s diseases [3,4].…”

Brain uptake of a non-radioactive pseudo-carrier and its effect on the biodistribution of [18F]AV-133 in mouse brain

“…In recent years, increasing numbers of radiopharmaceuticals and molecular imaging probes have been developed to image biochemical, physiological, and pathologic processes in vivo by the use of positron emission tomography/computed tomography (PET/CT) and singlephoto emission computed tomography/computed tomography (SPECT/CT) scanners [1][2][3][4][5]. Vesicular monoamine transporter type II (VMAT2), which is located on vesicle membranes in neurons, performs a secondary type of transport by storing and packaging the monoamine neurotransmitters into vesicles [6].…”