An one-pot two-step automated synthesis of [18F]T807 injection, its biodistribution in mice and monkeys, and a preliminary study in humans
Journal
PLoS ONE
Journal Volume
14
Journal Issue
7
Pages
e0217384
Date Issued
2019
Author(s)
Huang Y.-Y.
Tsai C.-L.
Hsieh H.-Y.
Chiu C.-H.
Wu C.-H.
KAI-YUAN TZEN
Cheng C.-Y.
Ma K.-H.
Shiue C.-Y.
Abstract
[18F]T807 is a potent tau protein imaging agent. In order to fulfill the demand from preclinical and clinical studies, we developed an automated one-pot two-step synthesis of this potent tau imaging agent and studied its stability, and dosimetry in mice and monkeys. We also conducted a preliminary study of this imaging agent in humans. Using this one-pot two-step method, the radiochemical yield (RCY) of [18F]T807 was 20.5 ± 6.1% (n = 15) at the end of bombardment (EOB) in a synthesis time of 70±5 min. The chemical and radiochemical purities were >90% and the specific activities were 151 ± 52 GBq/μmol. The quality of [18F]T807 synthesized by this method met the U.S. Pharmacopoeia (USP) criteria. The stability test showed that the [18F]T807 injection was stable at room temperature for up to 4 h after the end of synthesis (EOS). The estimated effective dose of the [18F]T807 injection extrapolated from monkeys was 19 μSv/MBq (n = 2), while the estimated effective doses of the [18F]T807 injection extrapolated from fasted and non-fasted mice were 123 ± 27 (n = 3) and 94 ± 19 (n = 4) μSv/MBq, respectively. This one-pot two-step automated method produced the [18F] T807 injection with high reproducibility and high quality. PET imaging and radiation dosimetry evaluation in mice and Formosan rock monkeys suggested that the [18F]T807 injection synthesized by this method is suitable for use in human PET imaging studies. Thus, this method could fulfill the demand for the [18F]T807 injection in both preclinical and clinical studies of tauopathies, especially for nearby study sites without cyclotrons. ? 2019 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
SDGs
Other Subjects
flortaucipir f 18; tau protein; 7-(6-fluoropyridin-3-yl)-5H-pyrido(4,3-b)indole; carboline derivative; contrast medium; Macaca cyclopis; radiopharmaceutical agent; tau protein; adult; animal experiment; animal tissue; Article; automation; clinical article; clinical study; controlled study; dosimetry; drug distribution; drug half life; drug structure; drug synthesis; effective dose (radiation); fasting; good manufacturing practice; Haplorhini; human; male; mouse; nonhuman; one pot synthesis; positron emission tomography; preclinical study; reliability; reproducibility; retention time; room temperature; tauopathy; Alzheimer disease; animal; bioavailability; blood; chemistry; diagnostic imaging; gene expression; genetics; Institute for Cancer Research mouse; intravenous drug administration; Macaca; middle aged; pathology; procedures; radiometry; synthesis; tissue distribution; Alzheimer Disease; Animals; Biological Availability; Carbolines; Contrast Media; Drug Evaluation, Preclinical; Gene Expression; Haplorhini; Humans; Injections, Intravenous; Macaca; Male; Mice; Mice, Inbred ICR; Middle Aged; Positron-Emission Tomography; Radiometry; Radiopharmaceuticals; tau Proteins; Tissue Distribution
Type
journal article