RT Journal Article SR Electronic T1 Preclinical Evaluation of 18F-JNJ64349311, a Novel PET Tracer for Tau Imaging JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 975 OP 981 DO 10.2967/jnumed.116.185199 VO 58 IS 6 A1 Lieven Declercq A1 Frederik Rombouts A1 Michel Koole A1 Katleen Fierens A1 Jonas Mariën A1 Xavier Langlois A1 José Ignacio Andrés A1 Mark Schmidt A1 Gregor Macdonald A1 Diederik Moechars A1 Wim Vanduffel A1 Thomas Tousseyn A1 Rik Vandenberghe A1 Koen Van Laere A1 Alfons Verbruggen A1 Guy Bormans YR 2017 UL http://jnm.snmjournals.org/content/58/6/975.abstract AB In this study, we have synthesized and evaluated 18F-JNJ64349311, a tracer with high affinity for aggregated tau (inhibition constant value, 8 nM) and high (≥500×) in vitro selectivity for tau over β-amyloid, in comparison with the benchmark compound 18F-AV1451 (18F-T807) in mice, rats, and a rhesus monkey. Methods: In vitro binding characteristics were determined for Alzheimer's disease, progressive supranuclear palsy, and corticobasal degeneration patient brain tissue slices using autoradiography studies. Ex vivo biodistribution studies were performed in mice. Radiometabolites were quantified in the brain and plasma of mice and in the plasma of a rhesus monkey using high-performance liquid chromatography. Dynamic small-animal PET studies were performed in rats and a rhesus monkey to evaluate tracer pharmacokinetics in the brain. Results: Mouse biodistribution studies showed moderate initial brain uptake and rapid brain washout. Radiometabolite analyses after injection of 18F-JNJ64349311 in mice showed the presence of a polar radiometabolite in plasma, but not in the brain. Semiquantitative autoradiography studies on postmortem tissue sections of human Alzheimer's disease brains showed highly displaceable binding to tau-rich regions. No specific binding was, however, found on human progressive supranuclear palsy and corticobasal degeneration brain slices. Small-animal PET scans of Wistar rats revealed moderate initial brain uptake (SUV, ∼1.5 at 1 min after injection) and rapid brain washout. Gradual bone uptake was, however, also observed. Blocking and displacement did not affect brain time–activity curves, suggesting no off-target specific binding of the tracer in the healthy rat brain. A small-animal PET scan of a rhesus monkey revealed moderate initial brain uptake (SUV, 1.9 at 1 min after injection) with a rapid washout. In the monkey, no bone uptake was detected during the 120-min scan. Conclusion: This biologic evaluation suggests that 18F-JNJ64349311 is a promising tau PET tracer candidate, with a favorable pharmacokinetic profile, as compared with 18F-AV1451.