Comparative studies of potential cancer biomarkers carbon-11 labeled MMP inhibitors (S)-2-(4′-[11C]methoxybiphenyl-4-sulfonylamino)-3- methylbutyric acid and N-hydroxy-(R)-2-[[(4′-[11C] methoxyphenyl)sulfonyl]benzylamino]-3-methylbutanamide

Qi-Huang Zheng, Xiangshu Fei, Xuan Liu, Ji Quan Wang, K. Lee Stone, Tanya D. Martinez, Dawn J. Gay, Winston L. Baity, Kathy Miller, George W. Sledge, Gary Hutchins

Research output: Contribution to journalArticle

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Abstract

(S)-2-(4′-[11C]methoxybiphenyl-4-sulfonylamino)-3- methylbutyric acid ([11C]MSMA) and N-hydroxy-(R)-2-[[(4′-[ 11C]methoxyphenyl)sulfonyl]benzylamino]-3-methylbutanamide ([ 11C]CGS 25966), carbon-11 labeled matrix metalloproteinase (MMP) inhibitors, have been synthesized for evaluation as new potential positron emission tomography (PET) cancer biomarkers. [11C]MSMA was prepared by appropriate precursor (S)-2-(4′-hydroxybiphenyl-4-sulfonylamino)-3- methylbutyric acid tert-butyl ester, which was synthesized in eight steps from amino acid (L)-valine in 39.4% chemical yield. This precursor was labeled by [11C]methyl triflate through O-[11C]methylation method at the hydroxyl position of biphenol under basic conditions, followed by a quick acid hydrolysis and isolated by solid-phase extraction (SPE) purification to produce pure target compound [11C]MSMA in 35-55% radiochemical yield, based on 11CO2, decay corrected to end of bombardment (EOB), and 20-25 min synthesis time. [11C]CGS 25966 was prepared in our previous work starting from amino acid (D)-valine. The biodistribution of [11C]MSMA and [11C]CGS 25966 were determined at 45 min post iv injection in breast cancer animal models MCF-7's transfected with IL-1α implanted athymic mice and MDA-MB-435 implanted athymic mice. The results showed the uptakes of [11C]MSMA and [11C]CGS 25966 in these tumors were 0.95 and 0.42%dose/g in MCF-7's transfected with IL-1α implanted mice, 0.98 and 1.53%dose/g in MDA-MB-435 implanted mice, respectively; the ratios of tumor/muscle (T/M) and tumor/blood (T/B) were 1.21 and 1.09 (T/M, MCF-7's), 0.99 and 0.84 (T/B, MCF-7's), 1.38 and 1.27 (T/M, MDA-MB-435), 1.27 and 1.95 (T/B, MDA-MB-435), respectively. The micro-PET images of [11C]MSMA and [11C]CGS 25966 in both breast cancer athymic mice were acquired for 15 min from a MCF-7's transfected with IL-1α and/or MDA-MB-435 implanted mouse at 45 min post iv injection of 1 mCi of the tracer using a dedicated high resolution (<3 mm full-width at half-maximum) small FOV (field-of-view) PET imaging system, Indy-PET II scanner, developed in our laboratory, which showed both tumors were invisible with both tracers. The results were compared. From our results, we concluded that both [11C]MSMA and [11C]CGS 25966 might be unsuitable as PET tracers for cancer imaging.

Original languageEnglish
Pages (from-to)77-85
Number of pages9
JournalNuclear Medicine and Biology
Volume31
Issue number1
DOIs
StatePublished - Jan 2004

Fingerprint

Matrix Metalloproteinase Inhibitors
Tumor Biomarkers
Carbon
Positron-Emission Tomography
Neoplasms
Interleukin-1
Nude Mice
Valine
Muscles
Breast Neoplasms
N-hydroxy-2-(((4'-methoxyphenyl)sulfonyl)benzylamino)-3-methylbutanamide
2-(4'-methoxybiphenyl-4-sulfonylamino)-3-methylbutyric acid
Amino Acids
Injections
Solid Phase Extraction
Hydroxyl Radical
Methylation
Esters
Hydrolysis
Animal Models

Keywords

  • (S)-2-(4′-[C]methoxybiphenyl-4- sulfonylamino)-3-methylbutyric acid
  • Cancer biomarkers
  • Carbon-11
  • Matrix metalloproteinase inhibitor
  • Positron emission tomography

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging

Cite this

Comparative studies of potential cancer biomarkers carbon-11 labeled MMP inhibitors (S)-2-(4′-[11C]methoxybiphenyl-4-sulfonylamino)-3- methylbutyric acid and N-hydroxy-(R)-2-[[(4′-[11C] methoxyphenyl)sulfonyl]benzylamino]-3-methylbutanamide. / Zheng, Qi-Huang; Fei, Xiangshu; Liu, Xuan; Wang, Ji Quan; Stone, K. Lee; Martinez, Tanya D.; Gay, Dawn J.; Baity, Winston L.; Miller, Kathy; Sledge, George W.; Hutchins, Gary.

In: Nuclear Medicine and Biology, Vol. 31, No. 1, 01.2004, p. 77-85.

Research output: Contribution to journalArticle

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title = "Comparative studies of potential cancer biomarkers carbon-11 labeled MMP inhibitors (S)-2-(4′-[11C]methoxybiphenyl-4-sulfonylamino)-3- methylbutyric acid and N-hydroxy-(R)-2-[[(4′-[11C] methoxyphenyl)sulfonyl]benzylamino]-3-methylbutanamide",
abstract = "(S)-2-(4′-[11C]methoxybiphenyl-4-sulfonylamino)-3- methylbutyric acid ([11C]MSMA) and N-hydroxy-(R)-2-[[(4′-[ 11C]methoxyphenyl)sulfonyl]benzylamino]-3-methylbutanamide ([ 11C]CGS 25966), carbon-11 labeled matrix metalloproteinase (MMP) inhibitors, have been synthesized for evaluation as new potential positron emission tomography (PET) cancer biomarkers. [11C]MSMA was prepared by appropriate precursor (S)-2-(4′-hydroxybiphenyl-4-sulfonylamino)-3- methylbutyric acid tert-butyl ester, which was synthesized in eight steps from amino acid (L)-valine in 39.4{\%} chemical yield. This precursor was labeled by [11C]methyl triflate through O-[11C]methylation method at the hydroxyl position of biphenol under basic conditions, followed by a quick acid hydrolysis and isolated by solid-phase extraction (SPE) purification to produce pure target compound [11C]MSMA in 35-55{\%} radiochemical yield, based on 11CO2, decay corrected to end of bombardment (EOB), and 20-25 min synthesis time. [11C]CGS 25966 was prepared in our previous work starting from amino acid (D)-valine. The biodistribution of [11C]MSMA and [11C]CGS 25966 were determined at 45 min post iv injection in breast cancer animal models MCF-7's transfected with IL-1α implanted athymic mice and MDA-MB-435 implanted athymic mice. The results showed the uptakes of [11C]MSMA and [11C]CGS 25966 in these tumors were 0.95 and 0.42{\%}dose/g in MCF-7's transfected with IL-1α implanted mice, 0.98 and 1.53{\%}dose/g in MDA-MB-435 implanted mice, respectively; the ratios of tumor/muscle (T/M) and tumor/blood (T/B) were 1.21 and 1.09 (T/M, MCF-7's), 0.99 and 0.84 (T/B, MCF-7's), 1.38 and 1.27 (T/M, MDA-MB-435), 1.27 and 1.95 (T/B, MDA-MB-435), respectively. The micro-PET images of [11C]MSMA and [11C]CGS 25966 in both breast cancer athymic mice were acquired for 15 min from a MCF-7's transfected with IL-1α and/or MDA-MB-435 implanted mouse at 45 min post iv injection of 1 mCi of the tracer using a dedicated high resolution (<3 mm full-width at half-maximum) small FOV (field-of-view) PET imaging system, Indy-PET II scanner, developed in our laboratory, which showed both tumors were invisible with both tracers. The results were compared. From our results, we concluded that both [11C]MSMA and [11C]CGS 25966 might be unsuitable as PET tracers for cancer imaging.",
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T1 - Comparative studies of potential cancer biomarkers carbon-11 labeled MMP inhibitors (S)-2-(4′-[11C]methoxybiphenyl-4-sulfonylamino)-3- methylbutyric acid and N-hydroxy-(R)-2-[[(4′-[11C] methoxyphenyl)sulfonyl]benzylamino]-3-methylbutanamide

AU - Zheng, Qi-Huang

AU - Fei, Xiangshu

AU - Liu, Xuan

AU - Wang, Ji Quan

AU - Stone, K. Lee

AU - Martinez, Tanya D.

AU - Gay, Dawn J.

AU - Baity, Winston L.

AU - Miller, Kathy

AU - Sledge, George W.

AU - Hutchins, Gary

PY - 2004/1

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N2 - (S)-2-(4′-[11C]methoxybiphenyl-4-sulfonylamino)-3- methylbutyric acid ([11C]MSMA) and N-hydroxy-(R)-2-[[(4′-[ 11C]methoxyphenyl)sulfonyl]benzylamino]-3-methylbutanamide ([ 11C]CGS 25966), carbon-11 labeled matrix metalloproteinase (MMP) inhibitors, have been synthesized for evaluation as new potential positron emission tomography (PET) cancer biomarkers. [11C]MSMA was prepared by appropriate precursor (S)-2-(4′-hydroxybiphenyl-4-sulfonylamino)-3- methylbutyric acid tert-butyl ester, which was synthesized in eight steps from amino acid (L)-valine in 39.4% chemical yield. This precursor was labeled by [11C]methyl triflate through O-[11C]methylation method at the hydroxyl position of biphenol under basic conditions, followed by a quick acid hydrolysis and isolated by solid-phase extraction (SPE) purification to produce pure target compound [11C]MSMA in 35-55% radiochemical yield, based on 11CO2, decay corrected to end of bombardment (EOB), and 20-25 min synthesis time. [11C]CGS 25966 was prepared in our previous work starting from amino acid (D)-valine. The biodistribution of [11C]MSMA and [11C]CGS 25966 were determined at 45 min post iv injection in breast cancer animal models MCF-7's transfected with IL-1α implanted athymic mice and MDA-MB-435 implanted athymic mice. The results showed the uptakes of [11C]MSMA and [11C]CGS 25966 in these tumors were 0.95 and 0.42%dose/g in MCF-7's transfected with IL-1α implanted mice, 0.98 and 1.53%dose/g in MDA-MB-435 implanted mice, respectively; the ratios of tumor/muscle (T/M) and tumor/blood (T/B) were 1.21 and 1.09 (T/M, MCF-7's), 0.99 and 0.84 (T/B, MCF-7's), 1.38 and 1.27 (T/M, MDA-MB-435), 1.27 and 1.95 (T/B, MDA-MB-435), respectively. The micro-PET images of [11C]MSMA and [11C]CGS 25966 in both breast cancer athymic mice were acquired for 15 min from a MCF-7's transfected with IL-1α and/or MDA-MB-435 implanted mouse at 45 min post iv injection of 1 mCi of the tracer using a dedicated high resolution (<3 mm full-width at half-maximum) small FOV (field-of-view) PET imaging system, Indy-PET II scanner, developed in our laboratory, which showed both tumors were invisible with both tracers. The results were compared. From our results, we concluded that both [11C]MSMA and [11C]CGS 25966 might be unsuitable as PET tracers for cancer imaging.

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KW - Cancer biomarkers

KW - Carbon-11

KW - Matrix metalloproteinase inhibitor

KW - Positron emission tomography

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