RT Journal Article
SR Electronic
T1 Quantification of cerebral 5-HT2A receptors by reference tissue kinetic analysis of [11C]MDL 100,907 PET
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 162
OP 162
VO 51
IS supplement 2
A1 Philipp Meyer
A1 Zubin Bhagwagar
A1 Philip Cowen
A1 Vincent Cunningham
A1 Paul Grasby
A1 Rainer Hinz
YR 2010
UL http://jnm.snmjournals.org/content/51/supplement_2/162.abstract
AB 162 Objectives [11C]MDL100,907 (MDL) is a promising PET ligand for cerebral 5-HT2A receptor quantification. Recent studies imply that MDL PET may be quantified by non-invasive reference tissue analyses with cerebellum as reference region. We explored the validity of such analyses. Methods Five healthy volunteers underwent two MDL PET studies at baseline and after mirtazapine 5-HT2A receptor blockade. Estimates of binding potential (BPnd) and receptor occupancy (Occ) of ten regions of interest (ROI) were obtained with: simplified reference tissue model (SRTM), multi-linear reference tissue model (MRTM), their two-parameter versions (SRTM2/MRTM2), Logan’s non-invasive graphical analysis (NIGA) and tissue activity concentration ratio (TR). NIGA was also used voxel-wise to generate parametric BPnd maps. A two-tissue compartment model analysis with arterial input function (2TCM) served as reference method (Hinz et al., JCBFM 2007). Results SRTM and MRTM frequently failed to yield reliable results. SRTM2 and MRTM2 gave almost identical estimates of BPnd, which highly correlated with 2TCM analyses (R2≥0.86) although with negative bias (-29±27% across all ROI at baseline). NIGA was less biased (-19±16%) and better correlated with 2TCM (R2≥0.93). Regarding Occ, NIGA and SRTM2/MRTM2 showed comparable biases (-11±27% vs. -7±47%) but correlation with 2TCM was higher for NIGA (R2=0.90 vs. 0.77). NIGA parametric maps resulted in moderate bias in BPnd (-26±22%; R2≥0.88) and Occ (-17±36%; R2=0.78). TR performed least favourably. Conclusions NIGA is well suited for analysis of MDL PET studies, yielding estimates of 5-HT2A receptor availability that are highly correlated with results from invasive 2TCM analyses. This greatly enhances the applicability of 5-HT2A receptor PET studies