PET imaging of serotonin transporters with [11C]DASB: test-retest reproducibility using a multilinear reference tissue parametric imaging method.
Parametric imaging of serotonin transporters (SERT) with 11C-labeled 3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)benzonitrile ([11C]DASB) PET is a useful data analysis tool. The purpose of this study was to evaluate the reproducibility of measurements of SERT binding potential (BP) and relative blood flow (R1) by a 2-parameter multilinear reference tissue parametric imaging method (MRTM2) for human [11C]DASB studies.


METHODS
Eight healthy subjects (3 men, 5 women; age, 26 +/- 9 y) underwent 2 [11C]DASB PET scans separated by 1 h on the same day (dose, 703 +/- 111 MBq). Parametric images of BP and R1 were generated by MRTM2 using the cerebellum as a reference region. The k'2 (clearance rate constant from the reference region) required by MRTM2 was estimated by the 3-parameter MRTM. Reproducibility of BP and R1 measurements was evaluated by calculating bias (100 x (retest - test/test), variability (SD of the bias), and reliability (intraclass correlation coefficient = rho) for several representative regions of interest (ROIs). BP and R1 were estimated for ROI time-activity curves fitted by MRTM2 and were compared with those based on the parametric images.


RESULTS
The test-retest (0.066 +/- 0.013/0.06 +/- 0.011 min(-1)) MRTM k'2 reproducibility was excellent with small bias (3%) and variability (6%) and high reliability (0.95). Retest BP values were consistently lower than those of test BP values in all regions (a mean negative bias of approximately 6%; P < 0.001). The test-retest BP variability was relatively small, ranging from 4% to 13%, with rho ranging from 0.44 to 0.85. In contrast to BP, test-retest R1 values were similar with negligible bias of < or =0.1%. The test-retest R1 variability was excellent and smaller than that of BP ranging from 3% to 6%, with rho ranging from 0.58 to 0.95. BP and R1 values estimated by the ROI time-activity curve-fitting method were slightly lower ( approximately 3% and approximately 1%, respectively) than those by the parametric imaging method (P < 0.001). However, the test-retest bias and variability of BP and R1 were very similar for both ROI and parametric methods.


CONCLUSIONS
Our results suggest that [11C]DASB parametric imaging of BP and R1 with the noninvasive MRTM2 method is reproducible and reliable for PET studies of SERT.
Kim
Jae Seung
JS
Molecular Imaging Branch, National Institute of Mental Health, Bethesda, Maryland, USA. jaeskim@smc.seoul.kr
Ichise
Masanori
M
Sangare
Janet
J
Innis
Robert B
RB
D000328:Adult; D000465:Algorithms; D000814:Aniline Compounds / Q000493:pharmacokinetics*; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D003198:Computer Simulation; D005260:Female; D006801:Humans; D007089:Image Enhancement / Q000379:methods*; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D016014:Linear Models; D008297:Male; D008954:Models, Biological; D049268:Positron-Emission Tomography / Q000379:methods* / Q000592:standards; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D012016:Reference Values; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D013440:Sulfides / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014481:United States
C412822:3-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile; D000814:Aniline Compounds; D019275:Radiopharmaceuticals; D050486:Serotonin Plasma Membrane Transport Proteins; D013440:Sulfides