Simplified quantification of 5-HT2A receptors in the human brain with [11C]MDL 100,907 PET and non-invasive kinetic analyses

Philipp T. Meyer, Zubin Bhagwagar, Philip J. Cowen, Vincent J. Cunningham, Paul M. Grasby, Rainer Hinz

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18 Citations (Scopus)

Abstract

Background: [C-11]MDL100,907 is a promising positron emission tomography (PET) ligand for 5-HT2A receptor quantification in vivo. Studies suggest that [C-11]MDL100,907 PET may be quantified by non-invasive reference tissue analyses using cerebellum as reference region. We systematically investigated the validity of such analyses. Methods: Five healthy volunteers underwent [C-11]MDL100,907 PET at baseline and after mirtazapine pre-treatment. Regional time-activity curves of 10 regions of interest (ROI) were analyzed for binding potential (BPND) and mirtazapine receptor occupancy (Occ) using: simplified reference tissue model (SRTM), multi-linear reference tissue model (MRTM), their two-parameter versions (SRTM2/MRTM2), non-invasive graphical analysis (NIGA) and a tissue activity concentration ratio. NIGA was also applied voxel-wise to generate BPND maps. These methods were compared with a two-tissue compartment model with arterial input function (2TCM) Results: SRTM and MRTM frequently failed to yield reliable results. SRTM2 and MRTM2 gave virtually identical estimates of BPND, which were highly correlated with 2TCM analyses (R-2 >= 0.86) although with negative bias (-29 +/- 27% at baseline across all ROI). NIGA was less biased (-19 +/- 16%) and better correlated with 2TCM (R-2 >= 0.93). Regarding Occ, NIGA and SRTM2/MRTM2 showed Comparable mean biases (-11 +/- 27% vs. -7 +/- 47%) but correlation with 2TCM was higher for NIGA (R-2 = 0.90 vs. 0.77). NIGA parametric maps (analysed using identical ROI) resulted in moderate bias in BPND (-26 +/- 22%; R-2 >= 0.88) and Occ (-17 +/- 36%: R-2 = 0.78). Estimates obtained from tissue ratios performed least favourably. Conclusions: NIGA is well suited for analysis of [C-11]MDL100,907 PET studies, yielding estimates of 5-HT2A receptor availability and changes that are highly correlated with results from invasive 2TCM analyses. This should greatly enhance the applicability of 5-HT2A receptor PET studies.

Original languageEnglish
Pages (from-to)984-993
Number of pages10
JournalNeuroimage
Volume50
Issue number3
Early online date18 Jan 2010
DOIs
Publication statusPublished - 15 Apr 2010

Keywords

  • [C-11]MDL 100,907
  • 5-HT2A receptor
  • positron emission tomography
  • tracer kinetic modelling
  • reference region
  • positron-emission-tomography
  • graphical analysis method
  • reference tissue model
  • living human-brain
  • serotonin receptors
  • binding
  • dopamine
  • ligand
  • neuroreceptor
  • radioligand

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