Investigating the reproducibility of the novel Alpha-5 GABAA receptor PET ligand [11C]Ro15 4513

Method: Four male healthy controls had two 90-minute dynamic PET scans on a Siemens/ECAT 962 scanner, each after intravenous injection of approximately 444 MBq (mean 432.9 MBq, range 359.3–452 MBq) of [C]Ro15 4513. Data was movement-corrected with a frame-to-frame coregistration method (Hammers et al. 2007) and co-registered with T1-wieghted structural 3D-images obtained on a 3 T magnetic resonance images (MRI). Arterial plasma input function (IFs) were obtained by continuous blood withdrawal for 15 min and combination with discrete plasma samples for correction of radio-labelled metabolites and incorporation of plasma-over-blood ratio within Clickfit Software (MRC Cyclotron Unit, Hammersmith, London, UK). The PET volumes-of-distribution (VD) were quantified using spectral analysis (SA) within RPM (Gunn et al, 1997). The default slow frequency boundary of 0.0008 s−1 in RPM (log10=−3.10) was changed to 0.00063 s−1 (log10=−3.2) in order to match the C decay constant of log10=−3.25 (Hammers et al, 2007). VDs from representative high and low binding regions were extracted via an automated region-of-interest (ROI) definition method (MAPER, Heckemann et al. 2010). Outcome measures were intraclass correlation coefficient (ICCs), the coefficient of variation (CV), and reliability in ROIs.