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Original article
MRI with hyperpolarised [1-13C]pyruvate detects advanced pancreatic preneoplasia prior to invasive disease in a mouse model
  1. Eva M Serrao1,2,
  2. Mikko I Kettunen1,2,3,
  3. Tiago B Rodrigues1,2,
  4. Piotr Dzien1,2,
  5. Alan J Wright1,2,
  6. Aarthi Gopinathan1,
  7. Ferdia A Gallagher1,4,
  8. David Y Lewis1,2,
  9. Kristopher K Frese5,
  10. Jaime Almeida1,
  11. William J Howat1,
  12. David A Tuveson6,
  13. Kevin M Brindle1,2
  1. 1Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK
  2. 2Department of Biochemistry, University of Cambridge, Cambridge, UK
  3. 3A.I.Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
  4. 4Department of Radiology, University of Cambridge, Cambridge, UK
  5. 5Princess Margaret Cancer Centre, Toronto, Ontario, Canada
  6. 6Cold Spring Harbor Laboratory, New York, New York, USA
  1. Correspondence to Professor Kevin M Brindle, Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1GA, UK; kmb1001{at}cam.ac.uk

Abstract

Objectives Pancreatic cancer (PCa) is treatable by surgery when detected at an early stage. Non-invasive imaging methods able to detect both established tumours and their precursor lesions are needed to select patients for surgery. We investigated here whether pancreatic preneoplasia could be detected prior to the development of invasive cancers in genetically engineered mouse models of PCa using metabolic imaging.

Design The concentrations of alanine and lactate and the activities of lactate dehydrogenase (LDH) and alanine aminotransferase (ALT) were measured in extracts prepared from the pancreas of animals at different stages of disease progression; from pancreatitis, through tissue with predominantly low-grade and then high-grade pancreatic intraepithelial neoplasia and then tumour. 13C magnetic resonance spectroscopic imaging (13C-MRSI) was used to measure non-invasively changes in 13C labelling of alanine and lactate with disease progression, following injection of hyperpolarised [1-13C]pyruvate.

Results Progressive decreases in the alanine/lactate concentration ratio and ALT/LDH activity ratio with disease progression were accompanied by a corresponding decrease in the [1-13C]alanine/[1-13C]lactate signal ratio observed in 13C-MRSI images of the pancreas.

Conclusions Metabolic imaging with hyperpolarised [1-13C]pyruvate enables detection and monitoring of the progression of PCa precursor lesions. Translation of this MRI technique to the clinic has the potential to improve the management of patients at high risk of developing PCa.

  • CANCER
  • MAGNETIC RESONANCE IMAGING
  • PANCREAS

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/

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