Error analysis for PET measurement of dopamine D2 receptor occupancy by antipsychotics with [11C]raclopride and [11C]FLB 457.
Dopamine D(2) receptor occupancy by antipsychotic drugs has been measured with positron emission tomography (PET) by comparing the binding potential (BP) values before and after drug administration. This occupancy has been found to be related to clinical effects and side effects. In this study, we evaluated the uncertainty of the quantitative analysis for estimating the dopamine D(2) receptor occupancy by antipsychotics in simulation and human studies of [(11)C]raclopride and for the high affinity ligand [(11)C]FLB 457. Time-activity curves of [(11)C]raclopride and [(11)C]FLB 457 were simulated, and the reliability of BP estimated by a simplified reference tissue model and the calculated occupancy were investigated for various noise levels, BP values, and scan durations. Then, in the human PET study with and without antipsychotics, the uncertainty of BP and occupancy estimates and the scan duration required for a reliable estimation were investigated by a bootstrap approach. Reliable and unbiased estimates of [(11)C]raclopride BP(ND) could be obtained with recording as short as 32 min, with the relative standard deviation (SD) of the striatal occupancy remaining less than 10%. Conversely, in [(11)C]FLB 457 studies, the mean value increased and SD of the temporal cortex and thalamus exceeded 10% when the scan duration was shorter than 60 min. These results demonstrated that dopamine D(2) receptor occupancy by antipsychotics can be estimated precisely with an optimal scan duration with [(11)C]raclopride and [(11)C]FLB 457.
Ikoma
Yoko
Y
Molecular Imaging Center, National Institute of Radiological Sciences 4-9-1, Anagawa, Inage-ku, Chiba, 263-8555, Japan.
Ito
Hiroshi
H
Arakawa
Ryosuke
R
Okumura
Masaki
M
Seki
Chie
C
Shidahara
Miho
M
Takahashi
Hidehiko
H
Kimura
Yuichi
Y
Kanno
Iwao
I
Suhara
Tetsuya
T
D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage*; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D006801:Humans; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D008297:Male; D011759:Pyrrolidines / Q000493:pharmacokinetics*; D020891:Raclopride / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D015203:Reproducibility of Results; D012457:Salicylamides / Q000493:pharmacokinetics*; D012680:Sensitivity and Specificity; D014018:Tissue Distribution
D014150:Antipsychotic Agents; D002250:Carbon Radioisotopes; D011759:Pyrrolidines; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2; D012457:Salicylamides; C065065:FLB 457; D020891:Raclopride