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Modeling Considerations for 11C-CUMI-101, an Agonist Radiotracer for Imaging Serotonin 1A Receptor In Vivo with PET

Matthew S. Milak, Alin J. Severance, R. Todd Ogden, Jaya Prabhakaran, J.S. Dileep Kumar, Vattoly J. Majo, J. John Mann and Ramin V. Parsey
Journal of Nuclear Medicine April 2008, 49 (4) 587-596; DOI: https://doi.org/10.2967/jnumed.107.046540

Article Figures & Data

Figures

  • FIGURE 1. 
    FIGURE 1. 

    (A) Fraction of plasma activity associated with unmetabolized 11C-CUMI-101 in baboon plasma during a single scan. Fitted line is estimated from the Hill model (1 − AtB/[tB + C]). (B) Total and metabolite-corrected plasma radioactivity. Fitted line represents the 3-exponential function fit to the data. Error bars represent weights calculated by the delta method.

  • FIGURE 2. 
    FIGURE 2. 

    Regional time–activity curves and corresponding least-squares minimized fits to 3 different models. (A) 2TCNI. (B) Basis pursuit. (C and D) LEGA (native and transformed space, respectively). CER = cerebellum; ACN = anterior cingulate; TEM = temporal cortex.

  • FIGURE 3. 
    FIGURE 3. 

    Modeling metrics comparing 2TCNI, basis pursuit, and LEGA models at 6 different scan durations. (A) PD. (B) WSMSS. (C) Variance. (D) ICC. (E) Identifiability. For all measures, medians are taken across all scans and all ROIs, for both subjects. (A) Error bars represent average deviation from the median. Asterisk in A indicates that the modeling of dorsal raphe did not converge for basis pursuit for the 100-min scan time (for a single study) and thus was left out of the analysis.

  • FIGURE 4. 
    FIGURE 4. 

    Mean percentage change (PD) in VT (A) and BPF (B) of 11C-CUMI-101 after blockade with 8-OH-DPAT and WAY-100635. Values were derived from the LEGA model with a 100-min scan duration. ACN = anterior cingulate; AMY = amygdala; CER = cerebellum; DRN = dorsal raphe; HIP = hippocampus; INS = insula; PFC = prefrontal cortex; TEM = temporal cortex.

  • FIGURE 5. 
    FIGURE 5. 

    (First row) Sagittal, coronal, and axial parametric PET images of 11C-CUMI-101 BPF values in baboon brain. (Second and third rows): PET images after blockade by 8-OH-DPAT and WAY-100635, respectively. (Fourth row) Corresponding coregistered MR images. On the MR images, the hippocampus has been highlighted.

  • FIGURE 6. 
    FIGURE 6. 

    Correlation plots of VT values across various modeling approaches including ROI-analysis vs. voxel-based analyses. (A) 2TCNI voxel vs. 2TCNI ROI (R2 = 0.97). (B) 2TCNI ROI vs. LEGA ROI (R2 = 0.97). (C) Basis pursuit ROI vs. LEGA ROI (R2 = 0.97). (D) 2TCNI voxel vs. LEGA ROI (R2 of 1.00). Line of identity has been added for reference. Data reflect all ROIs in all studies.

Tables

  • TABLE 1

    Time Stability Data for 3 Models Tested

    2TCNIBasis pursuitLEGA
    ROIVTBPVTBPVTBP
    ACN9090110100100100
    AMY80801201009090
    DRN11011012012010090
    HIP1101101101109090
    INS80701201009090
    PFC11010090908080
    TEM707090909080

    • ACN = anterior cingulate; AMY = amygdala; DRN = dorsal raphe; HIP = hippocampus; INS = insula; PFC = prefrontal cortex; TEM = temporal cortex.

    • Numbers indicate the shortest scan duration for which the average VT and BPF values from all test–retest experiments for each ROI were between 95% and 105% of the average value, when using 120-min scan duration and also when SD of these percentages is <10%.

  • TABLE 2

    Ranks of 3 Methods Used for Each Metric at 100-Minute Scanning Time*

    Metric2TCNILEGABasis
    PD213
    WSMSS213
    VAR213
    ICC222
    ID1N/A2

    • ↵* With 1 being the best of each criterion.

    • VAR = variance; ID = identifiability; N/A = not applicable.

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