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.
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 (31)P 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 (P(i)) and nucleoside triphosphates. However, after treatment with DMXAA, perfusion was reduced and the P(i)/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 P(i)/NTP ratio.
Beauregard
Daniel A
DA
Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, UK.
Pedley
R Barbara
RB
Hill
Sally A
SA
Brindle
Kevin M
KM
D000230:Adenocarcinoma / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D003287:Contrast Media; D019786:Gadolinium DTPA; D006801:Humans; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D016513:Mice, SCID; D013267:Stilbenes / Q000627:therapeutic use*; D014183:Transplantation, Heterologous; D014966:Xanthenes / Q000627:therapeutic use*; D044004:Xanthones
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D003287:Contrast Media; D013267:Stilbenes; D014966:Xanthenes; D044004:Xanthones; C066668:vadimezan; C058728:fosbretabulin; D019786:Gadolinium DTPA