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

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          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. [(11)C]-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.

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          Author and article information

          Journal
          Journal of Cerebral Blood Flow & Metabolism
          J Cereb Blood Flow Metab
          Springer Nature
          0271-678X
          1559-7016
          August 03 2011
          August 03 2011
          : 32
          : 1
          : 70-80
          Article
          10.1038/jcbfm.2011.108
          3323353
          21811290
          © 2011

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