Characterization of 3 novel tau radiopharmaceuticals,11C-RO-963,11C-RO-643, and18F-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 BrasicChakradhar Mishra, Madhav Thambisetty, Abhay Mogekar, Anil Mathur, Marilyn Albert, Robert F. Dannals, Edilio Borroni

Research output: Contribution to journalArticlepeer-review

66 Scopus citations


11C-RO-963,11C-RO-643, and18F-RO-948 (previously referred to as11C-RO6924963,11C-RO6931643, and18F-RO6958948, respectively) have been reported as promising PET tracers for tau imaging based on in vitro and preclinical PET data. Here we describe the first, to our knowledge, human evaluation of these novel radiotracers. Methods: Amyloid PET–positive Alzheimer disease (AD) subjects and younger controls each received 2 different tau tracers. Dynamic 90-min scans were obtained after bolus injection of11C-RO-963,11C-RO-643, or18F-RO-948. Arterial blood sampling was performed on 11 healthy controls and 11 AD subjects. Regions were defined on MR images, and PET data were quantified by plasma reference graphical analysis (for total distribution volume) and target cerebellum ratio (SUV ratios of 60- to 90-min frames). SUV ratio images were also analyzed voxelwise. Five older controls each underwent 2 scans with18F-RO-948 for evaluation of test–retest variability. Four AD subjects underwent a repeated18F-RO-948 scan 6–22 mo after the first scan. Six additional healthy controls (3 men and 3 women; age range, 41–67 y) each underwent 1 whole-body dosimetry scan with18F-RO-948. Results: In younger controls, SUVpeak was observed in the temporal lobe with values of approximately 3.0 for11C-RO-963, 1.5 for11C-RO-643, and 3.5 for18F-RO-948. Over all brain regions and subjects, the trend was for18F-RO-948 to have the highest SUVpeak, followed by11C-RO-963 and then11C-RO-643. Regional analysis of SUV ratio and total distribution volume for11C-RO-643 and18F-RO-948 clearly discriminated the AD group from the healthy control groups. Compartmental modeling confirmed that11C-RO-643 had lower brain entry than either11C-RO-963 or18F-RO-948 and that18F-RO-948 showed better contrast between (predicted) areas of high versus low tau accumulation. Thus, our subsequent analysis focused on18F-RO-948. Both voxelwise and region-based analysis of18F-RO-948 binding in healthy controls versus AD subjects revealed multiple areas where AD subjects significantly differed from healthy controls. Of 22 high-binding regions, 13 showed a significant group difference (after ANOVA, F(1,21) 5 45, P, 10-5). Voxelwise analysis also revealed a set of symmetric clusters where AD subjects had higher binding than healthy controls (threshold of P, 0.001, cluster size . 50). Conclusion:18F-RO-948 demonstrates characteristics superior to11C-RO-643 and11C-RO-963 for characterization of tau pathology in AD. Regional binding data and kinetic properties of18F-RO-948 compare favorably with other existing tau PET tracers.

Original languageEnglish
Pages (from-to)1869-1876
Number of pages8
JournalJournal of Nuclear Medicine
Issue number12
StatePublished - Dec 1 2018


  • Alzheimer disease
  • Molecular imaging
  • Novel radiotracers
  • PET
  • Radiotracer development
  • Tau


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