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


METHODS
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.
Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK Department of Biochemistry, University of Cambridge, Cambridge, UK.
Eva M
EM
Serrao
Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK Department of Biochemistry, University of Cambridge, Cambridge, UK A.I.Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Mikko I
MI
Kettunen
Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK Department of Biochemistry, University of Cambridge, Cambridge, UK.
Tiago B
TB
Rodrigues
Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK Department of Biochemistry, University of Cambridge, Cambridge, UK.
Piotr
P
Dzien
Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK Department of Biochemistry, University of Cambridge, Cambridge, UK.
Alan J
AJ
Wright
Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
Aarthi
A
Gopinathan
Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK Department of Radiology, University of Cambridge, Cambridge, UK.
Ferdia A
FA
Gallagher
Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK Department of Biochemistry, University of Cambridge, Cambridge, UK.
David Y
DY
Lewis
Princess Margaret Cancer Centre, Toronto, Ontario, Canada.
Kristopher K
KK
Frese
Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
Jaime
J
Almeida
Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.
William J
WJ
Howat
Cold Spring Harbor Laboratory, New York, New York, USA.
David A
DA
Tuveson
Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK Department of Biochemistry, University of Cambridge, Cambridge, UK.
Kevin M
KM
Brindle
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D066241:Carbon-13 Magnetic Resonance Spectroscopy / Q000379:methods*; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis* / Q000378:metabolism; D018450:Disease Progression; D051379:Mice; D008822:Mice, Transgenic; D010179:Pancreas / Q000378:metabolism* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D010195:Pancreatitis / Q000175:diagnosis / Q000378:metabolism; D011230:Precancerous Conditions / Q000175:diagnosis* / Q000378:metabolism; D019289:Pyruvic Acid
D015415:Biomarkers; D019289:Pyruvic Acid
CANCER; MAGNETIC RESONANCE IMAGING; PANCREAS