Effects of combretastatin on murine tumours monitored by 31P MRS, 1H MRS and 1H MRI

The effects of the vascular disrupting agents combretastatin A-4 disodium phosphate, 5,6-dimethylxanthenone-4-acetic acid and ZD6126 in a murine tumour: A comparative assessment using MRI and MRS

“…In general, the pH results followed the estimates of bioenergetic status, except for ZD6126 (200 mg/kg) where significant decreases in tumour pH were seen in the first hour after treatment despite their being no significant decrease in the b-NTP/Pi ratio. Apart from our earlier study with 100 mg/kg CA4DP [23], only one other study has reported on the effects of VDAs on tumour pH [40]. That was also performed using a 100 mg/kg dose of CA4DP and showed a significant pH decrease in the sarcoma F tumour within 30 minutes after treatment and some recovery by 150 minutes, a result that is not inconsistent with our findings.…”

“…Preliminary studies in this tumour model using a single dose of one VDA (100 mg/kg CA4DP) have previously been presented [23].…”

Pathophysiologic Effects of Vascular-Targeting Agents and the Implications for Combination with Conventional Therapies

“…Treatment with VDAs results in a significant and rapid decrease in extracellular pH (124). However, VDAs can also decrease intracellular pH (125)(126)(127), and this latter effect is also illustrated in Fig. 2.…”

Differential sensitivity of two adenocarcinoma xenografts to the anti‐vascular drugs combretastatin A4 phosphate and 5,6‐dimethylxanthenone‐4‐acetic acid, assessed using MRI and MRS

“…A reduction in tumour blood flow has been shown previously to result in increases in P i and decreases in NTP concentrations, presumably as a result of starvation of the tumour cells of essential nutrients such as oxygen and glucose. 5,18,26 However it must be emphasized that this is an indirect measurement of tumour perfusion, and while an increase in the P i /NTP ratio is consistent with a reduction in perfusion, no change in this ratio does not necessarily mean that perfusion has not been affected. For example, although HT29 tumours treated with hydralazine showed a reduction in blood volume, 27 the drug had little or no effect on the 31 P MR spectrum of the tumour.…”

“…15 Altered tumour blood flow in response to these antivascular therapies can be monitored as an increase in vascular resistance, 9 or by using relatively or truly noninvasive imaging techniques including autoradiography, 12 scintigraphy 16 and MRI. 5,17,18 We showed recently, using dynamic contrast agent-enhanced MRI (DCE-MRI), that the human colon adenocarcinoma, HT29, implanted in SCID mice, was relatively insensitive to treatment with CA4P for a period of up to 3 h. We also showed that drug response at 3 h was positively correlated with vascular permeability. 17 Since vascular permeability determined by MRI has been shown to be a surrogate marker for vascular endothelial growth factor (VEGF) expression and endothelial cell proliferation, [19][20][21] it suggested that the resistance of this tumour to CA4P may result from low VEGF expression and endothelial cell proliferation.…”