Measuring Receptor Occupancy with PET.
Author: Waarde, A.
Source: Current Pharmaceutical Design, Volume 6, Number 16, 1 November 2000 , pp. 1593-1610(18)
Publisher: Bentham Science Publishers
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Abstract:
Many physiological and biochemical measurements can be performed noninvasively in humans with modern imaging techniques like magnetic resonance imaging (MRI), positron emission tomography (PET) or single-photon emission computed tomography (SPECT). This review focuses on the monitoring of drug-receptor interactions in patients and healthy volunteers with PET. Such studies depend on the availability of a suitable radioligand; they are already possible for classical and atypical neuroleptics, anxiolytics, antidepressants, anticholinergics, antihistamines, antiepileptics, beta-blockers and hypnotic drugs. In Phase I-II human studies, measurements of plasma pharmacokinetics can be combined with images of receptor occupancy and be quantitatively related to pharmacologic effects which are induced in the same subjects. Optimal dosing schedules can be defined and valuable information for the design of Phase III studies can be acquired. Moreover, the effect of interventions (e.g. change of dose, additional medication) can be predicted. Medical imaging techniques will play an increasing role in clinical pharmacology and allow well-informed go/no-go decisions in future drug development.Keywords: Receptor Occupancy; Magnetic Resonanace Imaging; Single Photon emission computed tomography(SPECT); Receptor-rich regions; Neuroleptics; Neurotransmitter; Neuroimaging techniques; Serotonine antagonists; Muscarinc antagonist; Extrapyramidal symptoms(EPS); Antihistamines; Hypnotics; Pitfalls; Pseudo-equilibrium; Free Radioligand Concentration
Document Type: Review article
DOI: 10.2174/1381612003398951
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