TY - JOUR
T1 - Evaluation of18F-RO-948 PET for quantitative assessment of tau accumulation in the human brain
AU - Kuwabara, Hiroto
AU - Comley, Robert A.
AU - Borroni, Edilio
AU - Honer, Michael
AU - Kitmiller, Kelly
AU - Roberts, Joshua
AU - Gapasin, Lorena
AU - Mathur, Anil
AU - Klein, Gregory
AU - Wong, Dean F.
N1 - Publisher Copyright:
COPYRIGHT © 2018 by the Society of Nuclear Medicine and Molecular Imaging.
PY - 2018/12/1
Y1 - 2018/12/1
N2 - The availability of tau PET radioligands enables quantitative assessment of tau density and distribution in the human brain. We evaluated the kinetics of a novel radioligand,18F-RO-948 (previously referred to as18F-RO6958948), and its ability to identify tau positivity in individual patients with mild Alzheimer disease (AD). Methods: Eleven subjects with amyloid-positive mild AD, 5 amyloid-negative older control subjects (OC), and 5 younger control subjects (YC) completed 1 or 2 (4 AD and 5 OC) PET scans with18F-RO-948 for 90, 120, or 200 min. The kinetics of the radioligand was evaluated with standard compartmental and noncompartmental models (with plasma data in 70% of cases), tissue-reference methods, and SUV ratio. These approaches were applied to assess the ability of18F-RO-948 to discriminate AD subjects from OC subjects. Results: The plasma reference graphical analysis appeared to be the optimal method of quantification for18F-RO-948, yielding strictly time-consistent values of distribution volume and distribution volume ratio at 90 min against the analyses at 120 and 200 min. The reference tissue graphical analysis and SUV ratio were cross-validated against plasma reference graphical analysis. Test–retest evaluation showed excellent reproducibility. A proposed novel index of tau load, the regional tau-positive fraction, showed high values in the medial and lateral temporal and parietal regions in AD and successfully separated AD subjects from OC and YC subjects with a significant margin. Conclusion:18F-RO-948 appears to be a promising radioligand for quantitative imaging of tau in the brain of AD patients.
AB - The availability of tau PET radioligands enables quantitative assessment of tau density and distribution in the human brain. We evaluated the kinetics of a novel radioligand,18F-RO-948 (previously referred to as18F-RO6958948), and its ability to identify tau positivity in individual patients with mild Alzheimer disease (AD). Methods: Eleven subjects with amyloid-positive mild AD, 5 amyloid-negative older control subjects (OC), and 5 younger control subjects (YC) completed 1 or 2 (4 AD and 5 OC) PET scans with18F-RO-948 for 90, 120, or 200 min. The kinetics of the radioligand was evaluated with standard compartmental and noncompartmental models (with plasma data in 70% of cases), tissue-reference methods, and SUV ratio. These approaches were applied to assess the ability of18F-RO-948 to discriminate AD subjects from OC subjects. Results: The plasma reference graphical analysis appeared to be the optimal method of quantification for18F-RO-948, yielding strictly time-consistent values of distribution volume and distribution volume ratio at 90 min against the analyses at 120 and 200 min. The reference tissue graphical analysis and SUV ratio were cross-validated against plasma reference graphical analysis. Test–retest evaluation showed excellent reproducibility. A proposed novel index of tau load, the regional tau-positive fraction, showed high values in the medial and lateral temporal and parietal regions in AD and successfully separated AD subjects from OC and YC subjects with a significant margin. Conclusion:18F-RO-948 appears to be a promising radioligand for quantitative imaging of tau in the brain of AD patients.
KW - Alzheimer disease
KW - F-RO6958948 for tau imaging
KW - Neurology
KW - PET
KW - Radiotracer tissue kinetics
KW - Radiotracer tissue kinetics
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U2 - 10.2967/jnumed.118.214437
DO - 10.2967/jnumed.118.214437
M3 - Article
C2 - 30097505
AN - SCOPUS:85057585024
SN - 0161-5505
VL - 59
SP - 1877
EP - 1884
JO - Journal of Nuclear Medicine
JF - Journal of Nuclear Medicine
IS - 12
ER -