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

Dresselaers T, Theys J, Nuyts S, Wouters B, de Bruijn E, Anné J, Lambin P, Van Hecke P, Landuyt W - Br. J. Cancer (2003)

Bottom Line: 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.).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.

View Article: PubMed Central - PubMed

Affiliation: Biomedical NMR Unit, KU Leuven, Herestraat 49, 3000 Leuven, Belgium.

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.

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(A) In vivo 19F MRS spectrum obtained after 2 weeks (20 min/spectrum; TR=0.75 s; NS=1536) of a mouse treated with an i.v. injection of the TAPET-CD system (day 0) followed with an i.p. 5-FC injection (300 mg/kg). Spectrum obtained 2.5 h after 5-FC inoculation. (B) In vitro 19F MRS spectra of the perchloric acid extract of the whole tumour from the mouse in Figure 3A, snap-frozen immediately after the in vivo evaluation (TR=2.5 s; NA=12228; 1H decoupling).
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fig3: (A) In vivo 19F MRS spectrum obtained after 2 weeks (20 min/spectrum; TR=0.75 s; NS=1536) of a mouse treated with an i.v. injection of the TAPET-CD system (day 0) followed with an i.p. 5-FC injection (300 mg/kg). Spectrum obtained 2.5 h after 5-FC inoculation. (B) In vitro 19F MRS spectra of the perchloric acid extract of the whole tumour from the mouse in Figure 3A, snap-frozen immediately after the in vivo evaluation (TR=2.5 s; NA=12228; 1H decoupling).

Mentions: The potential clinical applicability of TAPET-CD/5-FC involves not only i.tu. application but also the systemic delivery of the enzyme/prodrug system. Intratumoural production of 5-FU following i.v. injection of TAPET-CD and i.p. injection of 5-FC (300 mg/kg) was measured in vivo in the HCT116 colon tumour (Figure 3AFigure 3


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

Dresselaers T, Theys J, Nuyts S, Wouters B, de Bruijn E, Anné J, Lambin P, Van Hecke P, Landuyt W - Br. J. Cancer (2003)

(A) In vivo 19F MRS spectrum obtained after 2 weeks (20 min/spectrum; TR=0.75 s; NS=1536) of a mouse treated with an i.v. injection of the TAPET-CD system (day 0) followed with an i.p. 5-FC injection (300 mg/kg). Spectrum obtained 2.5 h after 5-FC inoculation. (B) In vitro 19F MRS spectra of the perchloric acid extract of the whole tumour from the mouse in Figure 3A, snap-frozen immediately after the in vivo evaluation (TR=2.5 s; NA=12228; 1H decoupling).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2394413&req=5

fig3: (A) In vivo 19F MRS spectrum obtained after 2 weeks (20 min/spectrum; TR=0.75 s; NS=1536) of a mouse treated with an i.v. injection of the TAPET-CD system (day 0) followed with an i.p. 5-FC injection (300 mg/kg). Spectrum obtained 2.5 h after 5-FC inoculation. (B) In vitro 19F MRS spectra of the perchloric acid extract of the whole tumour from the mouse in Figure 3A, snap-frozen immediately after the in vivo evaluation (TR=2.5 s; NA=12228; 1H decoupling).
Mentions: The potential clinical applicability of TAPET-CD/5-FC involves not only i.tu. application but also the systemic delivery of the enzyme/prodrug system. Intratumoural production of 5-FU following i.v. injection of TAPET-CD and i.p. injection of 5-FC (300 mg/kg) was measured in vivo in the HCT116 colon tumour (Figure 3AFigure 3

Bottom Line: 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.).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.

View Article: PubMed Central - PubMed

Affiliation: Biomedical NMR Unit, KU Leuven, Herestraat 49, 3000 Leuven, Belgium.

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.

Show MeSH
Related in: MedlinePlus