Early effects of combretastatin A4 phosphate assessed by anatomic and carbogen-based functional magnetic resonance imaging on rat bladder tumors implanted in nude mice

Neoplasia. 2006 Jul;8(7):587-95. doi: 10.1593/neo.06232.

Abstract

Combretastatin A4 phosphate (CA4P) causes rapid disruption of the tumor vasculature and is currently being evaluated for antivascular therapy. We describe the initial results obtained with a noninvasive multiparametric magnetic resonance imaging (MRI) approach to assess the early effects of CA4P on rat bladder tumors implanted on nude mice. MRI (4.7 T) comprised a fast spin-echo sequence for growth curve assessment; a multislice multiecho sequence for T2 measurement before, 15 minutes after, and 24 hours after CA4P (100 mg/kg); and a fast T2w* gradient-echo sequence to assess MR signal modification under carbogen breathing before, 35 minutes after, and 24 hours after CA4P. The tumor fraction with increased T2w* signal intensity under carbogen (T+) was used to quantify CA4P effect on functional vasculature. CA4P slowed tumor growth over 24 hours and accelerated necrosis development. T+ decrease was observed already at 35 minutes post-CA4P. Early T2 increase was observed in regions becoming necrotic at 24 hours post-CA4P, as confirmed by high T2 and histology. These regions exhibited, under carbogen, a switch from T2w* signal increase before CA4P to a decrease postCA4P. The combination of carbogen-based functional MRI and T2 measurement may be useful for the early follow-up of antivascular therapy without the administration of contrast agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Carbon Dioxide / pharmacology*
  • Contrast Media / pharmacology
  • Magnetic Resonance Imaging / instrumentation*
  • Magnetic Resonance Imaging / methods*
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Neovascularization, Pathologic
  • Oxygen / pharmacology*
  • Radiation-Sensitizing Agents / pharmacology*
  • Rats
  • Stilbenes / pharmacology*
  • Time Factors
  • Urinary Bladder Neoplasms / metabolism
  • Urinary Bladder Neoplasms / pathology*

Substances

  • Antineoplastic Agents, Phytogenic
  • Contrast Media
  • Radiation-Sensitizing Agents
  • Stilbenes
  • Carbon Dioxide
  • carbogen
  • fosbretabulin
  • Oxygen