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MRI with hyperpolarised [1-13C]pyruvate detects advanced pancreatic preneoplasia prior to invasive disease in a mouse model.

Published version
Peer-reviewed

Repository DOI


Type

Article

Change log

Authors

Serrao, Eva M 
Kettunen, Mikko I 
Rodrigues, Tiago B 
Dzien, Piotr 
Wright, Alan J 

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. (13)C magnetic resonance spectroscopic imaging ((13)C-MRSI) was used to measure non-invasively changes in (13)C labelling of alanine and lactate with disease progression, following injection of hyperpolarised [1-(13)C]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-(13)C]alanine/[1-(13)C]lactate signal ratio observed in (13)C-MRSI images of the pancreas. CONCLUSIONS: Metabolic imaging with hyperpolarised [1-(13)C]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.

Description

Keywords

CANCER, MAGNETIC RESONANCE IMAGING, PANCREAS, Animals, Biomarkers, Carbon-13 Magnetic Resonance Spectroscopy, Carcinoma, Pancreatic Ductal, Disease Progression, Mice, Mice, Transgenic, Pancreas, Pancreatic Neoplasms, Pancreatitis, Precancerous Conditions, Pyruvic Acid

Journal Title

Gut

Conference Name

Journal ISSN

0017-5749
1468-3288

Volume Title

65

Publisher

BMJ
Sponsorship
Cancer Research Uk (None)
Cancer Research UK (CB4100)
Cancer Research UK (C14303/A17197)
Cancer Research Uk (None)
Cancer Research UK (17242)
Cancer Research UK (15678)
The work was supported by a Cancer Research UK Programme grant (17242) to K.M.B.. E.M.S. is a recipient of a fellowship from the European Union Seventh Framework Programme (FP7/2007-2013) under the Marie Curie Initial Training Network METAFLUX (project number 264780). T.B.R. is a recipient of an Intra- European Marie Curie (FP7-PEOPLE-2009-IEF, Imaging Lymphoma) fellowship and a Long-term European Molecular Biology Organization (EMBO-ALT-1145-2009) fellowship. E.M.S. and J.A. acknowledge the educational support of Programme for Advanced Medical Education from Calouste Gulbenkian Foundation, Champalimaud Foundation, Ministerio de Saude and Fundacao para a Ciencia e Tecnologia, Portugal. The polarizer and related materials were provided by GE Healthcare. The polarimeter was provided by NIHR Cambridge Biomedical Centre. The laboratory is a member of and receives support from the Cancer Research UK & Engineering and Physical Science Research Council Cancer Imaging Center in Cambridge and Manchester. The authors would also like to acknowledge Dr. Judit Espana, Dr. Athena Matakidou, Dr. Madhu Basetti, Dr. Jose Sandoval and Sarah McGuire for their help with experiments as well as the Tumor Models Core of Cancer Research UK-Cambridge Institute.