RT Journal Article
SR Electronic
T1 First in-human PET study of 3 novel tau radiopharmaceuticals: [11C]RO6924963, [11C]RO6931643, and [18F]RO6958948
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP jnumed.118.209916
DO 10.2967/jnumed.118.209916
A1 Wong, Dean F.
A1 Comley, Robert
A1 Kuwabara, Hiroto
A1 Rosenberg, Paul B.
A1 Resnick, Susan M
A1 Ostrowitzki, Susanne
A1 Vozzi, Cristina
A1 Boess, Frank
A1 Oh, Esther
A1 Lyketsos, Constantine G.
A1 Honer, Michael
A1 Gobbi, Luca
A1 Klein, Gregory
A1 George, Noble
A1 Gapasin, Lorena
A1 Kitzmiller, Kelly
A1 Roberts, Joshua
A1 Sevigny, Jeff
A1 Nandi, Ayon
A1 Brasic, James R
A1 Mishra, Chakradhar
A1 Thambisetty, Madhav
A1 Moghekar, Abhay
A1 Mathur, Anil
A1 Albert, Marilyn
A1 Dannals, Robert F
A1 Borroni, Edilio
YR 2018
UL http://jnm.snmjournals.org/content/early/2018/05/03/jnumed.118.209916.abstract
AB Background: [11C]RO-963, [11C]RO-643 and [18F]RO-948 (previously referred as [11C]RO6924963, [11C]RO6931643, and [18F]RO6958948, respectively) have been reported as promising PET tracers for tau imaging based on in vitro and preclinical PET data (1,2). Here we describe the first human evaluation of these novel radiotracers. Methods: Amyloid PET positive Alzheimer’s disease (AD) patients and young healthy subjects (YC) each received two different tau tracers. Dynamic 90 min scans were obtained after bolus injection of [11C]RO-963, [11C]RO-643 or [18F]RO-948. Arterial blood sampling was performed in 11 healthy controls (HC) and 11 AD. Regions were defined on MRI, and PET data were quantified by plasma reference graphical analysis (for VT) and target cerebellum ratio (SUVR60-90). SUVR images were also analyzed voxelwise. Five older healthy subjects (OC) each received two scans with [18F]RO-948 for evaluation of test-retest variability. Four AD subjects received a repeat [18F]RO-948 scan over about 1 year. Six additional HC (3M: 3F; 41-67y) each received one whole body dosimetry scan with [18F]RO-948. Results: In YC, peak SUV values were observed in the temporal lobe with values of approximately 3.0 for [11C]RO-963, 1.5 for [11C]RO-643 and 3.5 for [18F]RO-948. Over all brain regions and subjects, the trend was that [18F]RO-948 had the highest peak SUV value, followed by [11C]RO-963, and then [11C]RO-643. Regional analysis of SUVR and VT for [11C]RO-643 and [18F]RO-948 clearly discriminated AD and HC groups. Compartmental modeling confirmed that [11C]RO-643 had lower brain entry than both [18F]RO-963 and [18F]RO-948, and [18F]RO-948 showed a better contrast between (predicted) areas of high vs low tau accumulation. Thus, our subsequent analysis focused on [18F]RO-948. Both voxelwise and region-based analysis of [18F]RO-948 binding in HC vs AD revealed multiple areas where AD and HC significantly differed. Of 22 high-binding regions, 13 showed significant group difference (following ANOVA, F=45, p<10-5). Voxelwise analysis also revealed a set of symmetrical clusters where AD>HC (threshold of p<0.001, cluster size k>50). Conclusion: [18F]RO-948 demonstrates superior characteristics to [11C]RO-643 and [18F]RO-963 for characterization of tau pathology in AD. Regional binding data and kinetic properties of RO-948 compare favorably with existing other tau PET tracers.