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

被引:30
作者
Dresselaers, T
Theys, J
Nuyts, S
Wouters, B
de Bruijn, E
Anné, J
Lambin, P
Van Hecke, P
Landuyt, W
机构
[1] Katholieke Univ Leuven, Expt Radiobiol LEO, B-3000 Louvain, Belgium
[2] Katholieke Univ Leuven, Biomed NMR Unit, B-3000 Louvain, Belgium
[3] Univ Maastricht, MAASTRO Lab GROW, NL-6200 MD Maastricht, Netherlands
[4] Katholieke Univ Leuven, Expt Oncol Lab, B-3000 Louvain, Belgium
[5] Katholieke Univ Leuven, Rega Inst, Bacteriol Lab, B-3000 Louvain, Belgium
关键词
F-19; MRS; 5-fluorouracil; cytosine deaminase; xenograft human tumour; mouse; recombinant bacteria;
D O I
10.1038/sj.bjc.6601345
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The aim of this study was to evaluate the applicability of fluorine-19 magnetic resonance spectroscopy (F-19 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 F-19 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 F-19 MRS to monitor biologically-based treatments involving cytosine deaminase.
引用
收藏
页码:1796 / 1801
页数:6
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