Non-invasive 19F MR spectroscopy of 5-fluorocytosine to 5-fluorouracil conversion by recombinant Salmonella in tumours View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2003-11

AUTHORS

T Dresselaers, J Theys, S Nuyts, B Wouters, E de Bruijn, J Anné, P Lambin, P Van Hecke, W Landuyt

ABSTRACT

The aim of this study was to evaluate the applicability of fluorine-19 magnetic resonance spectroscopy ((19)F MRS) for monitoring in vivo the conversion of 5-fluorocytosine (5-FC) to 5-fluorouracil (5-FU) after using an attenuated Salmonella Typhimurium strain recombinant to provide cytosine deaminase (TAPET-CD). The (19)F MRS measurements were done on mice bearing the human colon tumour xenograft (HCT116). The intratumoural conversion is greater when TAPET-CD/5-FC is delivered intratumourally (i.tu.) than when TAPET-CD is delivered intravenously (i.v.) and 5-FC intraperitoneally (i.p.). Repeat measurements of the same tumour also yielded important information on the tumour colonization by TAPET-CD through the correlated 5-FC to 5-FU conversion efficacy. The in vivo MRS spectra were confirmed by in vitro (19)F MRS of perchloric acid extracts of the tumour tissue. No 5-FU metabolites were detectable in vivo in the tumours. However, the in vitro measurements revealed, besides 5-FC and 5-FU, the presence of small amounts of catabolites. Finally, spectra obtained in vitro from liver extracts of tumour-bearing mice treated i.tu. with TAPET-CD/5-FC showed no 5-FU and only little amounts of catabolites. Our data illustrate most importantly the potential of (19)F MRS to monitor biologically-based treatments involving cytosine deaminase. More... »

PAGES

6601345

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.bjc.6601345

DOI

http://dx.doi.org/10.1038/sj.bjc.6601345

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1034553324

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/14583786


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