Facile radiosynthesis of new carbon-11-labeled propanamide derivatives as selective androgen receptor modulator (SARM) radioligands for prostate cancer imaging

Mingzhang Gao, Min Wang, Kathy Miller, Qi-Huang Zheng

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The androgen receptor (AR) is an attractive target for the treatment and molecular imaging of prostate cancer. New carbon-11-labeled propanamide derivatives were first designed and synthesized as selective androgen receptor modulator (SARM) radioligands for prostate cancer imaging using the biomedical imaging technique positron emission tomography (PET). The target tracers, (S)-N-(4-cyano-3-(trifluoromethyl)phenyl)-2-hydroxy-3-(2-[ 11C] methoxyphenoxy)-2-methylpropanamide ([ 11C]8a), (S)-2-hydroxy-3-(2- [ 11C]methoxyphenoxy)-2-methyl-N-(4-nitro-3-(trifluoromethyl)phenyl) propanamide ([ 11C]8e), (S)-N-(4-cyano-3-(trifluoromethyl)phenyl)-2- hydroxy-3-(4-[ 11C]methoxyphenoxy)-2-methylpropanamide ([ 11C]8c) and (S)-2-hydroxy-3-(4-[ 11C]methoxyphenoxy)-2- methyl-N-(4-nitro-3-(trifluoromethyl)phenyl)propanamide ([ 11C]8g), were prepared by O-[ 11C]methylation of their corresponding precursors, (S)-N-(4-cyano-3-(trifluoromethyl)phenyl)-2-hydroxy-3-(2- hydroxyphenoxy)-2-methylpropanamide (9a), (S)-2-hydroxy-3-(2-hydroxyphenoxy)-2- methyl-N-(4-nitro-3-(trifluoromethyl)phenyl)propanamide (9b), (S)-N-(4-cyano-3-(trifluoromethyl)phenyl)-2-hydroxy-3-(4-hydroxyphenoxy) -2-methylpropanamide (9c) and (S)-2-hydroxy-3-(4-hydroxyphenoxy)-2-methyl-N-(4- nitro-3-(trifluoromethyl)phenyl)propanamide (9d), with [ 11C]CH 3OTf under basic conditions and isolated by a simplified C-18 solid-phase extraction (SPE) method in 55 ± 5% (n = 5) radiochemical yields based on [ 11C]CO 2 and decay corrected to end of bombardment (EOB). The overall synthesis time from EOB was 23 min, the radiochemical purity was >99%, and the specific activity at end of synthesis (EOS) was 277.5 ± 92.5 GBq/μmol (n = 5).

Original languageEnglish
Pages (from-to)1505-1512
Number of pages8
JournalSteroids
Volume76
Issue number13
DOIs
StatePublished - Dec 11 2011

Fingerprint

Flutamide
Androgen Receptors
Modulators
Prostatic Neoplasms
Carbon
Derivatives
Imaging techniques
Molecular imaging
Positron emission tomography
Molecular Imaging
Methylation
Solid Phase Extraction
Carbon Monoxide
Positron-Emission Tomography

Keywords

  • Androgen receptor (AR)
  • Carbon-11-labeled propanamide derivatives
  • Imaging
  • Positron emission tomography (PET)
  • Prostate cancer

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Molecular Biology
  • Organic Chemistry
  • Pharmacology

Cite this

@article{9c7ca8fe11fd443784c24c1ce4278956,
title = "Facile radiosynthesis of new carbon-11-labeled propanamide derivatives as selective androgen receptor modulator (SARM) radioligands for prostate cancer imaging",
abstract = "The androgen receptor (AR) is an attractive target for the treatment and molecular imaging of prostate cancer. New carbon-11-labeled propanamide derivatives were first designed and synthesized as selective androgen receptor modulator (SARM) radioligands for prostate cancer imaging using the biomedical imaging technique positron emission tomography (PET). The target tracers, (S)-N-(4-cyano-3-(trifluoromethyl)phenyl)-2-hydroxy-3-(2-[ 11C] methoxyphenoxy)-2-methylpropanamide ([ 11C]8a), (S)-2-hydroxy-3-(2- [ 11C]methoxyphenoxy)-2-methyl-N-(4-nitro-3-(trifluoromethyl)phenyl) propanamide ([ 11C]8e), (S)-N-(4-cyano-3-(trifluoromethyl)phenyl)-2- hydroxy-3-(4-[ 11C]methoxyphenoxy)-2-methylpropanamide ([ 11C]8c) and (S)-2-hydroxy-3-(4-[ 11C]methoxyphenoxy)-2- methyl-N-(4-nitro-3-(trifluoromethyl)phenyl)propanamide ([ 11C]8g), were prepared by O-[ 11C]methylation of their corresponding precursors, (S)-N-(4-cyano-3-(trifluoromethyl)phenyl)-2-hydroxy-3-(2- hydroxyphenoxy)-2-methylpropanamide (9a), (S)-2-hydroxy-3-(2-hydroxyphenoxy)-2- methyl-N-(4-nitro-3-(trifluoromethyl)phenyl)propanamide (9b), (S)-N-(4-cyano-3-(trifluoromethyl)phenyl)-2-hydroxy-3-(4-hydroxyphenoxy) -2-methylpropanamide (9c) and (S)-2-hydroxy-3-(4-hydroxyphenoxy)-2-methyl-N-(4- nitro-3-(trifluoromethyl)phenyl)propanamide (9d), with [ 11C]CH 3OTf under basic conditions and isolated by a simplified C-18 solid-phase extraction (SPE) method in 55 ± 5{\%} (n = 5) radiochemical yields based on [ 11C]CO 2 and decay corrected to end of bombardment (EOB). The overall synthesis time from EOB was 23 min, the radiochemical purity was >99{\%}, and the specific activity at end of synthesis (EOS) was 277.5 ± 92.5 GBq/μmol (n = 5).",
keywords = "Androgen receptor (AR), Carbon-11-labeled propanamide derivatives, Imaging, Positron emission tomography (PET), Prostate cancer",
author = "Mingzhang Gao and Min Wang and Kathy Miller and Qi-Huang Zheng",
year = "2011",
month = "12",
day = "11",
doi = "10.1016/j.steroids.2011.08.005",
language = "English",
volume = "76",
pages = "1505--1512",
journal = "Steroids",
issn = "0039-128X",
publisher = "Elsevier Inc.",
number = "13",

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T1 - Facile radiosynthesis of new carbon-11-labeled propanamide derivatives as selective androgen receptor modulator (SARM) radioligands for prostate cancer imaging

AU - Gao, Mingzhang

AU - Wang, Min

AU - Miller, Kathy

AU - Zheng, Qi-Huang

PY - 2011/12/11

Y1 - 2011/12/11

N2 - The androgen receptor (AR) is an attractive target for the treatment and molecular imaging of prostate cancer. New carbon-11-labeled propanamide derivatives were first designed and synthesized as selective androgen receptor modulator (SARM) radioligands for prostate cancer imaging using the biomedical imaging technique positron emission tomography (PET). The target tracers, (S)-N-(4-cyano-3-(trifluoromethyl)phenyl)-2-hydroxy-3-(2-[ 11C] methoxyphenoxy)-2-methylpropanamide ([ 11C]8a), (S)-2-hydroxy-3-(2- [ 11C]methoxyphenoxy)-2-methyl-N-(4-nitro-3-(trifluoromethyl)phenyl) propanamide ([ 11C]8e), (S)-N-(4-cyano-3-(trifluoromethyl)phenyl)-2- hydroxy-3-(4-[ 11C]methoxyphenoxy)-2-methylpropanamide ([ 11C]8c) and (S)-2-hydroxy-3-(4-[ 11C]methoxyphenoxy)-2- methyl-N-(4-nitro-3-(trifluoromethyl)phenyl)propanamide ([ 11C]8g), were prepared by O-[ 11C]methylation of their corresponding precursors, (S)-N-(4-cyano-3-(trifluoromethyl)phenyl)-2-hydroxy-3-(2- hydroxyphenoxy)-2-methylpropanamide (9a), (S)-2-hydroxy-3-(2-hydroxyphenoxy)-2- methyl-N-(4-nitro-3-(trifluoromethyl)phenyl)propanamide (9b), (S)-N-(4-cyano-3-(trifluoromethyl)phenyl)-2-hydroxy-3-(4-hydroxyphenoxy) -2-methylpropanamide (9c) and (S)-2-hydroxy-3-(4-hydroxyphenoxy)-2-methyl-N-(4- nitro-3-(trifluoromethyl)phenyl)propanamide (9d), with [ 11C]CH 3OTf under basic conditions and isolated by a simplified C-18 solid-phase extraction (SPE) method in 55 ± 5% (n = 5) radiochemical yields based on [ 11C]CO 2 and decay corrected to end of bombardment (EOB). The overall synthesis time from EOB was 23 min, the radiochemical purity was >99%, and the specific activity at end of synthesis (EOS) was 277.5 ± 92.5 GBq/μmol (n = 5).

AB - The androgen receptor (AR) is an attractive target for the treatment and molecular imaging of prostate cancer. New carbon-11-labeled propanamide derivatives were first designed and synthesized as selective androgen receptor modulator (SARM) radioligands for prostate cancer imaging using the biomedical imaging technique positron emission tomography (PET). The target tracers, (S)-N-(4-cyano-3-(trifluoromethyl)phenyl)-2-hydroxy-3-(2-[ 11C] methoxyphenoxy)-2-methylpropanamide ([ 11C]8a), (S)-2-hydroxy-3-(2- [ 11C]methoxyphenoxy)-2-methyl-N-(4-nitro-3-(trifluoromethyl)phenyl) propanamide ([ 11C]8e), (S)-N-(4-cyano-3-(trifluoromethyl)phenyl)-2- hydroxy-3-(4-[ 11C]methoxyphenoxy)-2-methylpropanamide ([ 11C]8c) and (S)-2-hydroxy-3-(4-[ 11C]methoxyphenoxy)-2- methyl-N-(4-nitro-3-(trifluoromethyl)phenyl)propanamide ([ 11C]8g), were prepared by O-[ 11C]methylation of their corresponding precursors, (S)-N-(4-cyano-3-(trifluoromethyl)phenyl)-2-hydroxy-3-(2- hydroxyphenoxy)-2-methylpropanamide (9a), (S)-2-hydroxy-3-(2-hydroxyphenoxy)-2- methyl-N-(4-nitro-3-(trifluoromethyl)phenyl)propanamide (9b), (S)-N-(4-cyano-3-(trifluoromethyl)phenyl)-2-hydroxy-3-(4-hydroxyphenoxy) -2-methylpropanamide (9c) and (S)-2-hydroxy-3-(4-hydroxyphenoxy)-2-methyl-N-(4- nitro-3-(trifluoromethyl)phenyl)propanamide (9d), with [ 11C]CH 3OTf under basic conditions and isolated by a simplified C-18 solid-phase extraction (SPE) method in 55 ± 5% (n = 5) radiochemical yields based on [ 11C]CO 2 and decay corrected to end of bombardment (EOB). The overall synthesis time from EOB was 23 min, the radiochemical purity was >99%, and the specific activity at end of synthesis (EOS) was 277.5 ± 92.5 GBq/μmol (n = 5).

KW - Androgen receptor (AR)

KW - Carbon-11-labeled propanamide derivatives

KW - Imaging

KW - Positron emission tomography (PET)

KW - Prostate cancer

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U2 - 10.1016/j.steroids.2011.08.005

DO - 10.1016/j.steroids.2011.08.005

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JO - Steroids

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SN - 0039-128X

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