The susceptibility of tumors to the antivascular drug combretastatin A4 phosphate correlates with vascular permeability.
The acute effects of the antivascular drug, combretastatin A4 phosphate, on tumor energy status and perfusion were assessed using magnetic resonance imaging (MRI) and spectroscopy. Localized (31)P magnetic resonance spectroscopy showed that LoVo and RIF-1 tumors responded well to drug treatment, with significant increases in the P(i)/nucleoside triphosphate ratio within 3 h, whereas SaS, SaF, and HT29 tumors did not respond to the same extent. This variable response was also seen in MRI experiments in which tumor perfusion was assessed by monitoring the kinetics of inflow of the contrast agent, gadolinium diethylenetriaminepentaacetate. These data were analyzed to give the initial rate and time constant for inflow of contrast agent and the integral under the inflow curve. The differential susceptibility of the tumors to combretastatin A4 phosphate showed a positive correlation with prior MRI measurements of tumor vascular permeability, which was determined by measuring the inflow of a macromolecular contrast agent, BSA-gadolinium diethylenetriaminepentaacetate.
Beauregard
D A
DA
Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, United Kingdom.
Hill
S A
SA
Chaplin
D J
DJ
Brindle
K M
KM
D000418:Albumins / Q000493:pharmacokinetics; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002199:Capillary Permeability / Q000502:physiology; D003287:Contrast Media / Q000493:pharmacokinetics; D005260:Female; D019786:Gadolinium DTPA / Q000493:pharmacokinetics; D006801:Humans; D018810:Magnetic Resonance Angiography; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D051379:Mice; D008808:Mice, Inbred CBA; D016513:Mice, SCID; D009374:Neoplasms, Experimental / Q000098:blood supply* / Q000188:drug therapy; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000503:physiopathology; D010758:Phosphorus; D013267:Stilbenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D000418:Albumins; D000972:Antineoplastic Agents, Phytogenic; D003287:Contrast Media; D013267:Stilbenes; C058946:albumin-(gadolinium-DTPA); D010758:Phosphorus; C058728:fosbretabulin; D019786:Gadolinium DTPA