The feasibility of assessing branched-chain amino acid metabolism in cellular models of prostate cancer with hyperpolarized [1-13C]-ketoisocaproate

Kelvin L. Billingsley, Jae Mo Park, Sonal Josan, Ralph Hurd, Dirk Mayer, Eleanor Spielman-Sun, Dwight G. Nishimura, James D. Brooks, Daniel Spielman

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Recent advancements in the field of hyperpolarized 13C magnetic resonance spectroscopy (MRS) have yielded powerful techniques capable of real-time analysis of metabolic pathways. These non-invasive methods have increasingly shown application in impacting disease diagnosis and have further been employed in mechanistic studies of disease onset and progression. Our goals were to investigate branched-chain aminotransferase (BCAT) activity in prostate cancer with a novel molecular probe, hyperpolarized [1-13C]-2-ketoisocaproate ([1-13C]-KIC), and explore the potential of branched-chain amino acid (BCAA) metabolism to serve as a biomarker. Using traditional spectrophotometric assays, BCAT enzymatic activities were determined in vitro for various sources of prostate cancer (human, transgenic adenocarcinoma of the mouse prostate (TRAMP) mouse and human cell lines). These preliminary studies indicated that low levels of BCAT activity were present in all models of prostate cancer but enzymatic levels are altered significantly in prostate cancer relative to healthy tissue. The MR spectroscopic studies were conducted with two cellular models (PC-3 and DU-145) that exhibited levels of BCAA metabolism comparable to the human disease state. Hyperpolarized [1-13C]-KIC was administered to prostate cancer cell lines, and the conversion of [1-13C]-KIC to the metabolic product, [1-13C]-leucine ([1-13C]-Leu), could be monitored via hyperpolarized 13C MRS.

Original languageEnglish (US)
Pages (from-to)791-795
Number of pages5
JournalMagnetic Resonance Imaging
Volume32
Issue number7
DOIs
StatePublished - Sep 2014
Externally publishedYes

Keywords

  • Branched-chain aminotransferase
  • Dynamic nuclear polarization
  • Hyperpolarized carbon-13
  • Magnetic resonance spectroscopy/spectroscopic imaging
  • Prostate cancer

ASJC Scopus subject areas

  • Biophysics
  • Biomedical Engineering
  • Radiology Nuclear Medicine and imaging

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