Objectives: Occupancy of dopamine D2 receptors by antipsychotic drugs can be estimated from reduction in the observed binding potential (BPND). Because BPND varies widely in occupancy studies, accuracy of the measurement of wide range BPND should be confirmed. The purpose of this study is to investigate errors in quantitative analysis for estimating dopamine D2 receptor occupancy by antipsychotics with agonist ligand [11C]MNPA which has high affinity and selectivity to dopamine D2 receptors1.\nMethods: Simulated TACs of [11C]MNPA with several noise levels were generated to investigate the bias and variation of parameter estimates caused by the statistical noise for non-linear least square (NLS) fitting and a simplified reference tissue model (SRTM) methods. A dynamic tracer concentrations was consisted of three target conditions (K1=0.44, k2=0.067, k3=0.02, 0.1 or 0.2, k4=0.18), and a reference (K1=0.44, k2=0.067) with a dynamic frame (20sec * 9, 1min * 5, 2min * 4, 4min * 11, 5min * 6, totally 90min) and a measured input function from human study1. Three true BPND values were assumed; 1.111 (baseline), 0.556 (occupancy = 50%) and 0.111 (90%). Then Gaussian noise was added at the noise level 1%, 3%, 5%, 7% and 10%, and five hundred noisy data sets were generated for each2. The reliability of BPND estimated by NLS and a SRTM and the calculated occupancy, dependency of scan durations (32, 44, 60, 75 and 90min) for SRTM were investigated. \nResults: For NLS and SRTM methods, the bias of estimated BPND values became larger as the noise level increased and these bias of BPND were larger than those of occupancy (Fig. 1A and 1B). In the case of small BPND, the bias became larger. For SRTM method, reliable and unbiased occupancy estimates of [11C]MNPA could be obtained by 60 min with the relative standard deviation remaining less than 10%. However, shorten scan duration depredate the quantification of very small binding potential (Fig1C).\nConclusions: Dopamine D2 receptor occupancy by antipsychotics can be estimated precisely by SRTM method with an optimal scan duration with [11C]MNPA. \nReference: [1] Otsuka T, 2008, Neuroimage, 41, suppl. 2, T134. [2] Ikoma Y, 2008, Neuroimage, 47, 43-50.[pic_01]Fig. 1 (A) Noise level dependency: Bias of BP and Occupancy estimated by NLS, (B) estimated by SRTM, (C) Scan Duration Dependency: Bias of BP and Occupancy at a 3% noise level estimated by SRTM.Brain\u2709 & BrainPET\u270
