McIntyre, Dominick J. O., Howe, Franklyn A., Ladroue, Christophe, Lofts, Fiona, Stubbs, Marion and Griffiths, John R. (2011) Can localised 19F magnetic resonance spectroscopy pharmacokinetics of 5FU in colorectal metastases predict clinical response? Cancer Chemotherapy and Pharmacology, Vol.68 (No.1). pp. 29-36. doi:10.1007/s00280-010-1438-2

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Abstract

Background 5-Fluorouracil remains widely used in
colorectal cancer treatment more than 40 years after its
development. 19F magnetic resonance spectroscopy can be
used in vivo to measure 5FU’s half-life and metabolism to
cytotoxic fluoronucleotides. Previous studies have shown
better survival associated with longer 5FU tumour half-life.
This work investigated 5FU pharmacokinetics in liver
metastases of colorectal cancer.
Methods A total of 32 subjects with colorectal cancer
undergoing 5FU treatment, 15 of whom had liver metastases,
were examined in a 1.5T MRI scanner, using a large
coil positioned over the liver. Non-localised spectra were
acquired in 1-min blocks for 32 min after injection of a
5FU bolus. The 5FU half-life was measured in each subject,
and averaged spectra were examined for the presence
of fluoronucleotides. Associations with progression-free
survival were assessed.
Results No association was observed between 5FU halflife,
tumour burden and survival. Half-lives were all shorter
than those associated with improved survival in the literature.
Remarkably, in the group with liver metastases, high
levels of fluoronucleotides were associated with poorer
survival; this counterintuitive result may be due to the
higher levels of fluoronucleotides (whose level is higher in
tumour tissue than in normal liver) in patients with higher
tumour burdens.
Conclusions It is recommended that future studies use
chemical shift imaging at higher field strengths to better
resolve tumour from normal liver. Non-localised spectroscopy
retains prognostic potential by enabling straightforward
detection of fluoronucleotides, which are present at
very low concentrations distributed throughout the tissue.

Item Type:	Journal Article
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions:	Faculty of Science > Statistics
Library of Congress Subject Headings (LCSH):	Colon (Anatomy) -- Cancer -- Treatment, Rectum -- Cancer -- Treatment, Fluorouracil, Metastasis
Journal or Publication Title:	Cancer Chemotherapy and Pharmacology
Publisher:	Springer
ISSN:	0344-5704
Official Date:	2011
Dates:	Date Event 2011 Published
Volume:	Vol.68
Number:	No.1
Page Range:	pp. 29-36
DOI:	10.1007/s00280-010-1438-2
Status:	Peer Reviewed
Access rights to Published version:	Open Access
Funder:	University of Cambridge, Cancer Research UK (CRUK), Hutchison Whampoa Ltd.

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