Comparison of New Tau PET-Tracer Candidates With [¹⁸F]T808 and [¹⁸F]T807

Abstract

Early clinical results of two tau tracers, [18F]T808 and [18F]T807, have recently been reported. In the present study, the biodistribution, radiometabolite quantification, and competition-binding studies were performed in order to acquire comparative preclinical data as well as to establish the value of T808 and T807 as benchmark compounds for assessment of binding affinities of eight new/other tau tracers. Biodistribution studies in mice showed high brain uptake and fast washout. In vivo radiometabolite analysis using high-performance liquid chromatography showed the presence of polar radiometabolites in plasma and brain. No specific binding of [18F]T808 was found in transgenic mice expressing mutant human P301L tau. In semiquantitative autoradiography studies on human Alzheimer disease slices, we observed more than 50% tau selective blocking of [18F]T808 in the presence of 1 µmol/L of the novel ligands. This study provides a straightforward comparison of the binding affinity and selectivity for tau of the reported radiolabeled tracers BF-158, BF-170, THK5105, lansoprazole, astemizole, and novel tau positron emission tomography ligands against T807 and T808. Therefore, these data are helpful to identify structural requirements for selective interaction with tau and to compare the performance of new highly selective and specific radiolabeled tau tracers.

Preclinical Evaluation of18F-JNJ64349311, a Novel PET Tracer for Tau Imaging

“…The precursor for radiosynthesis of 18 F-AV1451 and the authentic reference material and the nonradioactive reference material for AV680 and AV45 were synthesized by Janssen Research and Development (Janssen Pharmaceutica NV, Beerse, Belgium) according to literature reports (13). All other chemicals and reagents were purchased from commercial sources and used without further purification.…”

“…Data were acquired and analyzed using a GINA Star data acquisition system (Raytest). Quantification of radioactivity in samples of biodistribution and radiometabolite studies was performed according to a previously reported procedure (13). Quantitative data are expressed as mean 6 SD.…”

“…18 F-fluoride ( 18 F 2 ) was produced and purified according to a previously described procedure (13). A solution of 0.5 mg of trimethylammonium precursor (mono-or tris-trifluoroacetate salts) in 0.3 mL of dimethylformamide was added to the dried 18 F 2 /K 2 CO 3 /K-222 residue, and the mixture was heated at 120°C for 10 min.…”

“…Ultraviolet detection was performed at 254 nm. 18 F-AV1451 was radiolabeled according to a previously reported procedure (13).…”

“…Biodistribution studies were performed in healthy male Naval Medical Research Institute (NMRI) mice (body weight, 30-40 g) at 2, 10, 30, and 60 min after injection (n 5 3/time point) according to a previously reported procedure (13). SUVs were calculated as (counts per minute in body part/weight of the body part in g)/(sum of counts per minute in all body parts/body weight in g).…”