Research ArticleNeurology

Characterization of 3 Novel Tau Radiopharmaceuticals, 11C-RO-963, 11C-RO-643, and 18F-RO-948, in Healthy Controls and in Alzheimer Subjects

Dean F. Wong, Robert A. Comley, Hiroto Kuwabara, Paul B. Rosenberg, Susan M. Resnick, Susanne Ostrowitzki, Cristina Vozzi, Frank Boess, Esther Oh, Constantine G. Lyketsos, Michael Honer, Luca Gobbi, Gregory Klein, Noble George, Lorena Gapasin, Kelly Kitzmiller, Josh Roberts, Jeff Sevigny, Ayon Nandi, James Brasic, Chakradhar Mishra, Madhav Thambisetty, Abhay Moghekar, Anil Mathur, Marilyn Albert, Robert F. Dannals and Edilio Borroni
Journal of Nuclear Medicine December 2018, 59 (12) 1869-1876; DOI: https://doi.org/10.2967/jnumed.118.209916

Article Figures & Data

Figures

  • FIGURE 1.
    FIGURE 1.

    Line plots of time–activity curves in SUV of selected brain regions of 11C-RO-963 (A and D), 11C-RO-643 (B and E), and 18F-RO-948 (C and F) for YCs (panels A–C) and AD subjects (panels D–F).

  • FIGURE 2.
    FIGURE 2.

    Sagittal SUVR images of candidate radioligands, applied to same AD subjects and YCs. Cb = cerebellar cortex.

  • FIGURE 3.
    FIGURE 3.

    Scatterplots of SUVR vs. DVR for 11C-RO-643 (A) and SUVR data for 11CRO-643 vs. 18F-RO-948 for subjects who had both scans (B). Scatterplots of DVR (reference tissue graphical analysis [RTGA]) for 90- vs. 120-min circulation times for data analysis (C) and SUVR vs. DVR for 18F-RO-948 (D).

  • FIGURE 4.
    FIGURE 4.

    (A) Surface projection maps of mean 18F-RO-948 SUVR images of left and right hemispheres of AD subjects (from top to bottom: lateral, medial, and ventral views). (B) Box plot of SUVR data comparing AD subjects and OCs in 8 regions in which AD subjects showed highest mean SUVRs, as well as 3 Braak anterior regions (hippocampus, entorhinal area, and parahippocampus). Dots represent points lying outside ±2.7 SDs, assuming normal distributions. ER = entorhinal area; FO = frontal operculum; Fs = fusiform gyrus; Hp = hippocampus; IC = isthmus/cingulate; iPa = inferior parietal lobe; iTp = inferior temporal lobe; lOc = lateral occipital lobe; mFr = middle frontal lobe; mTp = middle temporal cortex; PH = parahippocampus; pCg = posterior cingulate gyrus; Pr = precuneus; sPa = superior parietal lobe; rFr = rostral frontal lobe; SM = supramarginal gyrus.

  • FIGURE 5.
    FIGURE 5.

    (A–D) Two roughly symmetrical SPM clusters (AD > OC) overlaid on 3 orthogonal views of standard MRI. (E) Line plots of volumes (across 1-cm-thick coronal slices) of over-the-threshold voxels of SPM analysis, hippopotamus, and amygdala along anterior–posterior axis. The 2 blue vertical lines indicate extent of anterior slice of Braak anterior block (19). (F–K) Clusters of high 18F-RO-948 tau-positive frequencies (>7 of 11 AD subjects) that spatially agreed with the 2 SPM clusters (F–H). Additional high-frequency clusters were noted in precuneus and posterior cingulate gyrus (I), and in superior and inferior parietal lobes, and supramarginal gyrus (J and K).

  • FIGURE 6.
    FIGURE 6.

    Checkerboard plot showing 18F-RO-948-positivity results (black cells: bilaterally positive; gray cells: unilaterally positive) of anterior and posterior Braak regions (19), and estimated Braak stages (right column) (20). esV =extrastriatal visual cortex; Fs = fusiform gyrus; Hp = hippocampus; mTp = middle temporal cortex; prV = primary visual cortex; sTp = superior temporal cortex; tER = transentorhinal cortex.

  • FIGURE 7.
    FIGURE 7.

    SUVR-cerebellar cortex images of 18F-RO-948 for all 11 AD subjects, arranged in descending order of global mean SUVR, alongside corresponding Aβ image (11C-Pittsburgh compound B SUVR, except for subjects AD02, AD05, and AD13, who had 18F-AV45 scans).

Tables

  • TABLE 1

    Study Design and Subject Demographics

    ControlAD
    PartRadioligandSubjectPlasma data (+)Age ± SD (y)SubjectPlasma data (+)Age ± SD (y)
    111C-RO-9632 (1F)230 ± 312 (1F)167 ± 69
    11C-RO-64322
    11C-RO-6432 (0F)225 ± 265 (2F)275.0 ± 7.8
    18F-RO-94824
    11C-RO-9633 (1F)332 ± 380
    18F-RO-9482
    2A18F-RO-9485 (0F)462 ± 85 (1F)364.0 ± 6
    Test–retest43
    2B18F-RO-9486 (3F)NA58 ± 9
    Dosimetry
  • TABLE 2

    Presence or Absence of Separation and Statistical Differences

    ParameterSideHpERPHmFrPrlOcFsSMmTpiTpiPa
    Separation*LeftPresentAbsentPresentAbsentAbsentAbsentPresentAbsentPresentAbsentAbsent
    RightAbsentPresentPresentAbsentAbsentAbsentAbsentAbsentAbsentAbsentAbsent
    Statistical differences†LeftAbsentPresentPresentPresentAbsentAbsentPresentAbsentPresentPresentAbsent
    RightPresentPresentPresentAbsentAbsentAbsentPresentAbsentPresentPresentPresent

    • ↵* AD > maximal OC.

    • ↵† AD > OC; Mann–Whitney test.

    • Hp = hippocampus; ER = entorhinal area; PH = parahippocampus; mFr = middle frontal lobe; Pr = precuneus; lOc = lateral occipital lobe; Fs = fusiform gyrus; SM = supramarginal gyrus; mTp = middle temporal cortex; iTp = inferior temporal lobe; iPa = inferior parietal lobe.

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