Metabolic imaging of pancreatic ductal adenocarcinoma detects altered choline metabolism

Marie France Penet, Tariq Shah, Santosh Bharti, Balaji Krishnamachary, Dmitri Artemov, Yelena Mironchik, Flonne Wildes, Anirban Maitra, Zaver M. Bhujwalla

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and lethal disease that develops relatively symptomfree and is therefore advanced at the time of diagnosis. The absence of early symptoms and effective treatments has created a critical need for identifying and developing new noninvasive biomarkers and therapeutic targets. Experimental Design: We investigated the metabolism of a panel of PDAC cell lines in culture and noninvasively in vivo with 1H magnetic resonance spectroscopic imaging (MRSI) to identify noninvasive biomarkers and uncover potential metabolic targets. Results: We observed elevated choline-containing compounds in the PDAC cell lines and tumors. These elevated choline-containing compounds were easily detected by increased total choline (tCho) in vivo, in spectroscopic images obtained from tumors. Principal component analysis of the spectral data identified additional differences in metabolites between immortalized human pancreatic cells and neoplastic PDAC cells. Molecular characterization revealed overexpression of choline kinase (Chk)-α, choline transporter 1 (CHT1), and choline transporter- like protein 1 (CTL1) in the PDAC cell lines and tumors. Conclusions: Collectively, these data identify new metabolic characteristics of PDAC and reveal potential metabolic targets. Total choline detected with 1H MRSI may provide an intrinsic, imaging probe-independent biomarker to complement existing techniques in detecting PDAC. The expression of Chk-α, CHT1, and CTL1 may provide additional molecular markers in aspirated cytological samples.

Original languageEnglish (US)
Pages (from-to)386-395
Number of pages10
JournalClinical Cancer Research
Volume21
Issue number2
DOIs
StatePublished - Jan 15 2015

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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