Dataset Information

PET imaging of brain aromatase in humans and rhesus monkeys by ¹¹C-labeled cetrozole analogs.

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 [¹¹C]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 corresponding ¹¹C-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 the ¹¹C-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 each ¹¹C-labeled analog to aromatase in the rhesus monkey brain. A human PET study using [¹¹C]iso-analog showed a similar distribution pattern of binding as that of [¹¹C]cetrozole. The time-activity curves showed that elimination of [¹¹C]iso-cetrozole from brain tissue was faster than that of ¹¹C-cetrozole, indicating more rapid metabolism of [¹¹C]iso-cetrozole. [¹¹C]Cetrozole has preferable metabolic stability for brain aromatase imaging in humans, although [¹¹C]iso-cetrozole might also be useful to measure aromatase level in living human brain because of its high binding potential.

SUBMITTER: Takahashi K

PROVIDER: S-EPMC8654920 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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PET imaging of brain aromatase in humans and rhesus monkeys by 11C-labeled cetrozole analogs.

Takahashi Kayo K Hosoya Takamitsu T Onoe Kayo K Mori Tomoko T Tazawa Shusaku S Mawatari Aya A Wada Yasuhiro Y Watanabe Yumiko Y Doi Hisashi H Watanabe Yasuyoshi Y

Scientific reports 20211208 1

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 [11C]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 corresponding 11C-labeled ...[more]

PMID: 34880350

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Dataset Information

PET imaging of brain aromatase in humans and rhesus monkeys by ¹¹C-labeled cetrozole analogs.

Publications

PET imaging of brain aromatase in humans and rhesus monkeys by <sup>11</sup>C-labeled cetrozole analogs.

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