1. PET imaging of brain aromatase in humans and rhesus monkeys by 11 C-labeled cetrozole analogs.
- Author
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Takahashi K, Hosoya T, Onoe K, Mori T, Tazawa S, Mawatari A, Wada Y, Watanabe Y, Doi H, and Watanabe Y
- Subjects
- Animals, Brain enzymology, Humans, Macaca mulatta, Male, Aniline Compounds administration & dosage, Aromatase metabolism, Brain diagnostic imaging, Carbon Radioisotopes administration & dosage, Positron-Emission Tomography methods, Triazoles administration & dosage
- Abstract
Aromatase is an estrogen synthetic enzyme that plays important roles in brain functions. To quantify aromatase expression in the brain by positron emission tomography (PET), we had previously developed [
11 C]cetrozole, which showed high specificity and affinity. To develop more efficient PET tracer(s) for aromatase imaging, we synthesized three analogs of cetrozole. We synthesized meta-cetrozole, nitro-cetrozole, and iso-cetrozole, and prepared the corresponding11 C-labeled tracers. The inhibitory activities of these three analogs toward aromatase were evaluated using marmoset placenta, and PET imaging of brain aromatase was performed using the11 C-labeled tracers in monkeys. The most promising analog in the monkey study, iso-cetrozole, was evaluated in the human PET study. The highest to lowest inhibitory activity of the analogs toward aromatase in the microsomal fraction from marmoset placenta was in the following order: iso-cetrozole, nitro-cetrozole, cetrozole, and meta-cetrozole. This order showed good agreement with the order of the binding potential (BP) of each11 C-labeled analog to aromatase in the rhesus monkey brain. A human PET study using [11 C]iso-analog showed a similar distribution pattern of binding as that of [11 C]cetrozole. The time-activity curves showed that elimination of [11 C]iso-cetrozole from brain tissue was faster than that of11 C-cetrozole, indicating more rapid metabolism of [11 C]iso-cetrozole. [11 C]Cetrozole has preferable metabolic stability for brain aromatase imaging in humans, although [11 C]iso-cetrozole might also be useful to measure aromatase level in living human brain because of its high binding potential., (© 2021. The Author(s).)- Published
- 2021
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