title: PET imaging of serotonin transporters with [11C]DASB: test-retest reproducibility using a multilinear reference tissue parametric imaging method.
abstract: 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.
authors.affiliation: Molecular Imaging Branch, National Institute of Mental Health, Bethesda, Maryland, USA. jaeskim@smc.seoul.kr
authors.forename: Jae Seung
authors.initials: JS
authors.lastname: Kim
authors.forename: Masanori
authors.initials: M
authors.lastname: Ichise
authors.forename: Janet
authors.initials: J
authors.lastname: Sangare
authors.forename: Robert B
authors.initials: RB
authors.lastname: Innis
mesh_terms: 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
chemical_list: C412822:3-amino-4-(2-dimethylaminomethylphenylsulfanyl)benzonitrile; D000814:Aniline Compounds; D019275:Radiopharmaceuticals; D050486:Serotonin Plasma Membrane Transport Proteins; D013440:Sulfides