Measuring drug occupancy in the absence of a reference region: the Lassen plot re-visited

J Cereb Blood Flow Metab. 2010 Jan;30(1):46-50. doi: 10.1038/jcbfm.2009.190. Epub 2009 Sep 9.

Abstract

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.

MeSH terms

  • Algorithms
  • Brain / diagnostic imaging*
  • Humans
  • Image Processing, Computer-Assisted
  • Monte Carlo Method
  • Pharmaceutical Preparations / metabolism*
  • Piperazines / metabolism
  • Positron-Emission Tomography
  • Pyridines / metabolism
  • Receptor, Serotonin, 5-HT1A / drug effects
  • Receptors, Drug / metabolism*
  • Serotonin Antagonists / metabolism

Substances

  • Pharmaceutical Preparations
  • Piperazines
  • Pyridines
  • Receptors, Drug
  • Serotonin Antagonists
  • Receptor, Serotonin, 5-HT1A
  • N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide