Test–retest reliability of the novel 5-HT1B receptor PET radioligand [11C]P943
[11C]P943 is a novel, highly selective 5-HT1B PET radioligand. The aim of this study was to determine the test–retest reliability of [11C]P943 using two different modeling methods and to perform a power analysis with each quantification technique.
Seven healthy volunteers underwent two PET scans on the same day. Regions of interest (ROIs) were the amygdala, hippocampus, pallidum, putamen, insula, frontal, anterior cingulate, parietal, temporal and occipital cortices, and cerebellum. Two multilinear radioligand quantification techniques were used to estimate binding potential: MA1, using arterial input function data, and the second version of the multilinear reference tissue model analysis (MRTM2), using the cerebellum as the reference region. Between-scan percent variability and intraclass correlation coefficients (ICC) were used to assess test–retest reliability. We also performed power analyses to determine the method that would allow the least number of subjects using within-subject or between-subject study designs. A voxel-wise ICC analysis for MRTM2 BPND was performed for the whole brain and all the ROIs studied.
Mean percent variability between two scans across regions ranged between 0.4 % and 12.4 % for MA1 BPND, 0.5 % and 11.5 % for MA1 BPP, 16.7 % and 28.3 % for MA1 BPF, and between 0.2 % and 5.4 % for MRTM2 BPND. The power analyses showed a greater number of subjects were required using MA1 BPF compared with other outcome measures for both within-subject and between-subject study designs. ICC values were the highest using MRTM2 BPND and the lowest with MA1 BPF in ten ROIs. Small regions and regions with low binding had lower ICC values than large regions and regions with high binding.
Reliable measures of 5-HT1B receptor binding can be obtained using the novel PET radioligand [11C]P943. Quantification of 5-HT1B receptor binding with MRTM2 BPND and with MA1 BPP provided the least variability and optimal power for within-subject and between-subject designs.
KeywordsSerotonin 5-HT1B Positron emission tomography Graphical analysis
- 4.McKusick VA, Kniffin CL, Hamosh A, Black JLI. 5-hydroxytryptamine receptor 1B; HTR1b. OMIM: Online Mendelian Inheritance in Man. Entry no. 182131. Johns Hopkins University, Baltimore, MD. http://www.omim.org/entry/182131.
- 17.First MB, Spitzer RL, Gibbon M, Williams JBW. Structured clinical interview for DSM-IV axis I disorders: clinician version (SCID-CV). Washington, DC: American Psychiatric Press; 1997.Google Scholar
- 18.Carson RE, Barker WC, Liow J-S, Johnson CA. Design of a motion-compensation OSEM list-mode algorithm for resolution-recovery reconstruction of the HRRT. Nucl Sci Symp Conf Record IEEE. 2003;5:3281–5.Google Scholar
- 27.Lenth RV (2006-9) Java applets for power and aample size. http://www.stat.uiowa.edu/~rlenth/Power. Accessed 10 Nov 2014.
- 32.Nabulsi NB, Huang Y, Ropchan JR, Cosgrove KP, Staley J, Planeta-Wilson B, et al. Synthesis and evaluation of [11C]P943 for 5-HT1B receptor studies in primates and humans. Presented at the Joint Molecular Imaging Conference, 8–11 September 2007, Providence, RI.Google Scholar
- 34.Parsey RV, Slifstein M, Hwang DR, Abi-Dargham A, Simpson N, Mawlawi O, et al. Validation and reproducibility of measurement of 5-HT1A receptor parameters with [carbonyl-11C]WAY-100635 in humans: comparison of arterial and reference tisssue input functions. J Cereb Blood Flow Metab. 2000;20(7):1111–33.CrossRefPubMedGoogle Scholar