Design and synthesis of carbon-11-labeled dual aromatase–steroid sulfatase inhibitors as new potential PET agents for imaging of aromatase and steroid sulfatase expression in breast cancer

Wang, Min; Mickens, Jarrett; Gao, Mingzhang; Miller, Kathy D.; Sledge, George W.; Hutchins, Gary D.; Zheng, Qi

doi:10.1016/j.steroids.2009.06.006

Cited by 17 publications

(6 citation statements)

References 24 publications

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“…Interestingly, there have been reports focusing upon the design of 11 C-labeled radiopharmaceuticals both for 43 to study angiogenesis 201 and related to the DASI concept to study aromatase and STS expression using PET. 202,203 These will be of particular utility once these other classes of compound enter formal clinical trials.…”

Section: Journal Of Medicinal Chemistrymentioning

confidence: 99%

Discovery and Development of the Aryl O-Sulfamate Pharmacophore for Oncology and Women’s Health

Thomas

Potter

2015

J. Med. Chem.

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In 1994, following work from this laboratory, it was reported that estrone-3-O-sulfamate irreversibly inhibits a new potential hormone-dependent cancer target steroid sulfatase (STS). Subsequent drug discovery projects were initiated to develop the core aryl O-sulfamate pharmacophore that, over some 20 years, have led to steroidal and nonsteroidal drugs in numerous preclinical and clinical trials, with promising results in oncology and women's health, including endometriosis. Drugs have been designed to inhibit STS, e.g., Irosustat, as innovative dual-targeting aromatase-steroid sulfatase inhibitors (DASIs) and as multitargeting agents for hormone-independent tumors, such as the steroidal STX140 and nonsteroidal counterparts, acting inter alia through microtubule disruption. The aryl sulfamate pharmacophore is highly versatile, operating via three distinct mechanisms of action, and imbues attractive pharmaceutical properties. This Perspective gives a personal view of the work leading both to the therapeutic concepts and these drugs, their current status, and how they might develop in the future.

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Section: Journal Of Medicinal Chemistrymentioning

confidence: 99%

Discovery and Development of the Aryl O-Sulfamate Pharmacophore for Oncology and Women’s Health

Thomas

Potter

2015

J. Med. Chem.

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“…Up to now, using 11 Cvorozole, the distribution of aromatase in the brain of rats, rhesus monkeys (16), baboons (17), and humans (18) and the effect of anabolic-androgenic steroids on aromatase (19,20) have been demonstrated. Although 11 C-labeled sulfonanilide analogs (21), 11 C-labeled sulfamate derivatives (dual aromatase-steroid sulfatase inhibitors) (22), and 11 C-letrozole (23) have also been developed as aromatase imaging PET probes, 11 C-vorozole is still the most popular probe for imaging brain aromatase. However, 11 C-vorozole has some drawbacks.…”

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confidence: 99%

¹¹C-Cetrozole: An Improved C-¹¹C-Methylated PET Probe for Aromatase Imaging in the Brain

Takahashi¹,

Hosoya

Onoe³

et al. 2014

J Nucl Med

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Aromatase (an enzyme that converts androgens to estrogens) in the brain is involved in neuroprotection, synaptic plasticity, and regulation of sexual and emotional behaviors. To investigate the physiologic and pathologic importance of aromatase in the brain, including in humans, we here report the development of a novel PET probe for aromatase, 11 C-cetrozole, which allows noninvasive quantification of aromatase expression. Methods: 11 C-cetrozole was synthesized by the C-11 C-methylation method developed by our group. In vitro autoradiography of frozen sections and a binding study with rat brain homogenates were conducted to demonstrate the specific binding and the dissociation constant. PET studies with anesthetized rhesus monkeys were performed to analyze the dynamics in the brain. Results: In vitro and in vivo studies using 11 C-cetrozole showed its superiority in brain aromatase imaging in terms of specificity and selectivity, compared with previously developed 11 C-vorozole. PET studies showed that 11 C-cetrozole had a higher signal-to-noise ratio, providing a sharper image than 11 C-vorozole, because the radioactive metabolite of 11 C-vorozole was taken up into the brain. High specific binding of 11 C-cetrozole was observed in the amygdala and hypothalamus, and we also noted binding in the nucleus accumbens of rhesus monkeys for the first time. Conclusion: These results suggest that PET imaging with newly developed 11 C-cetrozole is suitable for quantifying the expression of brain aromatase in vivo, possibly providing critical information regarding the functional roles of aromatase in human neurologic and emotional disorders.

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“…Some reports showed that STS inhibitor combined with aromatase inhibitor enhanced the response of hormonedependent breast cancer to the hormonal therapy [33,37] . A series of dual aromatase-sulfatase inhibitors (DASIs) were developed based on the aromatase inhibitor YM511, in order to explore the potential advantage of dual inhibition by a single agent [38] .…”

Section: Discussionmentioning

confidence: 99%

Shu-Gan-Liang-Xue decoction simultaneously down-regulates expressions of aromatase and steroid sulfatase in estrogen receptor positive breast cancer cells

2011

Chin. J. Cancer Res.

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Design and synthesis of carbon-11-labeled dual aromatase–steroid sulfatase inhibitors as new potential PET agents for imaging of aromatase and steroid sulfatase expression in breast cancer

Cited by 17 publications

References 24 publications

Discovery and Development of the Aryl O-Sulfamate Pharmacophore for Oncology and Women’s Health

Discovery and Development of the Aryl O-Sulfamate Pharmacophore for Oncology and Women’s Health

¹¹C-Cetrozole: An Improved C-¹¹C-Methylated PET Probe for Aromatase Imaging in the Brain

Shu-Gan-Liang-Xue decoction simultaneously down-regulates expressions of aromatase and steroid sulfatase in estrogen receptor positive breast cancer cells

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Design and synthesis of carbon-11-labeled dual aromatase–steroid sulfatase inhibitors as new potential PET agents for imaging of aromatase and steroid sulfatase expression in breast cancer

Cited by 17 publications

References 24 publications

Discovery and Development of the Aryl O-Sulfamate Pharmacophore for Oncology and Women’s Health

Discovery and Development of the Aryl O-Sulfamate Pharmacophore for Oncology and Women’s Health

11C-Cetrozole: An Improved C-11C-Methylated PET Probe for Aromatase Imaging in the Brain

Shu-Gan-Liang-Xue decoction simultaneously down-regulates expressions of aromatase and steroid sulfatase in estrogen receptor positive breast cancer cells

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Product

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¹¹C-Cetrozole: An Improved C-¹¹C-Methylated PET Probe for Aromatase Imaging in the Brain