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 D. Miller, George W. Sledge, Gary D. Hutchins

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52 Scopus citations

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

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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

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