Measuring Drug Occupancy in the Absence of a Reference Region: The Lassen Plot Re-Visited

• Published in: Journal of cerebral blood flow and metabolism Vol. 30; no. 1; pp. 46 - 50
• Main Authors: Cunningham, Vincent J, Rabiner, Eugenii A, Slifstein, Mark, Laruelle, Marc, Gunn, Roger N
• Format: Journal Article
• Language: English
• Published: London, England SAGE Publications 01.01.2010; Nature Publishing Group; Sage Publications Ltd
• Subjects: Algorithms; Biological and medical sciences; Brain - diagnostic imaging; Brief Communication; Drug toxicity and drugs side effects treatment; Humans; Image Processing, Computer-Assisted; Medical sciences; Miscellaneous (drug allergy, mutagens, teratogens...); Monte Carlo Method; Neurology; Pharmaceutical Preparations - metabolism; Pharmacology. Drug treatments; Piperazines - metabolism; Positron-Emission Tomography; Pyridines - metabolism; Receptor, Serotonin, 5-HT1A - drug effects; Receptors, Drug - metabolism; Serotonin Antagonists - metabolism; Vascular diseases and vascular malformations of the nervous system; occupancy; PET; graphical analysis; Nervous system diseases; Central nervous system disease; Positron emission tomography; Cerebrovascular disease; Cerebral disorder; Emission tomography
• ISSN: 0271-678X; 1559-7016; 1559-7016
• DOI: 10.1038/jcbfm.2009.190

Quantitative estimation of neuroreceptor occupancy by exogenous drugs using positron emission tomography is based on the reduction in the total volume of distribution (VT) of site-specific radioligands after drug administration. An estimate of the distribution volume of free and nonspecifically bound radioligand (VND) is also required to distinguish specific from total binding. However, a true reference region, devoid of specific binding, is often not available. We present a transformation of a graphical method, originally introduced by Lassen, using regional estimates of VT alone to determine occupancy, together with an extension that does not require baseline data.