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

Abstract

The effects of two anti-vascular agents, combretastatin A4 phosphate (CA4P), and 5,6-dimethylxanthenone-4-acetic acid (DMXAA), on the perfusion of two human colon adenocarcinomas implanted in SCID mice, were assessed for up to 3 h using non-invasive magnetic resonance imaging (MRI) and spectroscopy techniques (MRS). MRI measurements of GdDTPA inflow showed that treatment with CA4P had little effect on the perfusion of HT29 tumours. Localized 31P MRS measurements also showed that the drug had no significant effect on tumour cell energy status, as assessed from the ratio of the integrals of the signals from inorganic phosphate (Pi) and nucleoside triphosphates. However, after treatment with DMXAA, perfusion was reduced and the Pi/NTP ratio increased, indicating that the HT29 tumour is susceptible to the action of this drug. The LS174T tumour model was susceptible to both CA4P and DMXAA, using the criteria of changes in GdDTPA inflow and Pi/NTP ratio. Copyright © 2002 John Wiley & Sons, Ltd.