Measuring drug occupancy in the absence of a reference region: the Lassen plot re-visited.
Quantitative estimation of neuroreceptor occupancy by exogenous drugs using positron emission tomography is based on the reduction in the total volume of distribution (V(T)) of site-specific radioligands after drug administration. An estimate of the distribution volume of free and nonspecifically bound radioligand (V(ND)) 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 V(T) alone to determine occupancy, together with an extension that does not require baseline data.
Cunningham
Vincent J
VJ
GlaxoSmithKline, Clinical Imaging Centre, Hammersmith Hospital, London, UK. vincent.j.cunningham@gsk.com
Rabiner
Eugenii A
EA
Slifstein
Mark
M
Laruelle
Marc
M
Gunn
Roger N
RN
D000465:Algorithms; D001921:Brain / Q000000981:diagnostic imaging*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D009010:Monte Carlo Method; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010879:Piperazines / Q000378:metabolism; D049268:Positron-Emission Tomography; D011725:Pyridines / Q000378:metabolism; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects; D011955:Receptors, Drug / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000378:metabolism
D004364:Pharmaceutical Preparations; D010879:Piperazines; D011725:Pyridines; D011955:Receptors, Drug; D012702:Serotonin Antagonists; D044282:Receptor, Serotonin, 5-HT1A; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide