Table 1. Median parameter values for 5-FU metabolism determined by in vivo19F MRS of tumour-bearing mice.
Cmaxb |
AUCc |
||||
---|---|---|---|---|---|
Median (min, max) |
Median (min, max) |
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Metab. | Tumour | 5-FU | 5-FU+carbogen | 5-FU | 5-FU+carbogen |
5-FU | C26-B | 0.98 (0.44, 3.01) | 0.78 (0.51, 1.61) | 39 (15, 72) | 34 (13, 77) |
C26-10 | 0.78 (0.38, 2.95) | 1 (0.45, 2.07) | 27 (11, 80) | 38 (17, 85) | |
P=0.82 | P=0.63 | ||||
Anab. | C26-B | 0.35 (0, 0.59) | 0.36 (0.21, 0.50) | 20 (0, 34) | 25 (9, 35) |
C26-10 | 0.65 (0.31, 2.81) | 0.59 (0.45, 2.07) | 50 (20, 190) | 48 (33, 139) | |
P=0.0004 | P=0.0001 | ||||
Catab. | C26-B | 0.51 (0, 3.58) | 0.36 (0, 0.76) | 17 (0, 129) | 14 (0, 31) |
C26-10 | 0.35 (0, 3.56) | 0.32 (0, 0.57) | 13 (0, 96) | 11 (0, 24) | |
P=0.23 | P=0.36 | ||||
5-FU t1/2 (min)d | |||||
C26-B | 25.5 (17, 51) | 25.5 (8.5, 51) | |||
C26-10 | 25.5 (8.5, 42.5) | 34 (25.5, 34) | |||
P=0.51 |
Balb-C mice bearing murine colon carcinoma (s.c.) were examined by 19F MRS following a bolus injection of 150 mg kg−1 5-FU (C26-B, n=11; C26-10, n=15) or following 5-FU treatment combined with 9.5 min carbogen breathing (C26-B, n=11; C26-10; n=9). Pharmacokinetic parameters were evaluated for 5-FU, the total NMR-detectable anabolite pool, and the sum of the catabolites FUPA+FBAL. Two-way ANOVA was performed with transformed data (skewed distributions, see Materials and Methods) and gave the P values shown for the main effect of tumour type; for the main effect of carbogen, P>0.05 was found in all cases.
Cmax=mean of max tissue concentration in arbitrary relative units, determined from 19F signal integrals normalised to constant tissue volume using the 1 H signal from tissue water.
AUC=area under the concentration–time curve (from 0 to 119 min), normalised to constant tissue volume.
t1/2=half-life of 5-FU (time for decay from Cmax to 50% of Cmax).