Quantification of ligand PET studies using a reference region with a displaceable fraction: Application to occupancy studies with 11C-DASB as an example

Federico E. Turkheimer, Sudhakar Selvaraj, Rainer Hinz, Venkatesha Murthy, Zubin Bhagwagar, Paul Grasby, Oliver Howes, Lula Rosso, Subrata K. Bose

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

This paper aims to build novel methodology for the use of a reference region with specific binding for the quantification of brain studies with radioligands and positron emission tomography (PET). In particular: (1) we introduce a definition of binding potential BP D DVR-1 where DVR is the volume of distribution relative to a reference tissue that contains ligand in specifically bound form, (2) we validate a numerical methodology, rank-shaping regularization of exponential spectral analysis (RS-ESA), for the calculation of BP D that can cope with a reference region with specific bound ligand, (3) we demonstrate the use of RS-ESA for the accurate estimation of drug occupancies with the use of correction factors to account for the specific binding in the reference. 11C-DASB with cerebellum as a reference was chosen as an example to validate the methodology. Two data sets were used; four normal subjects scanned after infusion of citalopram or placebo and further six test-retest data sets. In the drug occupancy study, the use of RS-ESA with cerebellar input plus corrections produced estimates of occupancy very close the ones obtained with plasma input. Test-retest results demonstrated a tight linear relationship between BP D calculated either with plasma or with a reference input and high reproducibility.

Original languageEnglish (US)
Pages (from-to)70-80
Number of pages11
JournalJournal of Cerebral Blood Flow and Metabolism
Volume32
Issue number1
DOIs
StatePublished - Jan 2012

Keywords

  • [ C]-DASB
  • kinetic modelling
  • occupancy
  • positron emission tomography
  • rank-shaping spectral analysis
  • reference region
  • spectral analysis

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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