title: Early effects of combretastatin A4 phosphate assessed by anatomic and carbogen-based functional magnetic resonance imaging on rat bladder tumors implanted in nude mice.
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.
authors.affiliation: INSERM, U759, Orsay F-91405, France. carole.thomas@curie.u-psud.fr
authors.forename: Carole D
authors.initials: CD
authors.lastname: Thomas
authors.forename: Christine
authors.initials: C
authors.lastname: Walczak
authors.forename: Julia
authors.initials: J
authors.lastname: Kaffy
authors.forename: Renée
authors.initials: R
authors.lastname: Pontikis
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Jouanneau
authors.forename: Andreas
authors.initials: A
authors.lastname: Volk
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002245:Carbon Dioxide / Q000494:pharmacology*; D003287:Contrast Media / Q000494:pharmacology; D008279:Magnetic Resonance Imaging / Q000295:instrumentation* / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D010100:Oxygen / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D051381:Rats; D013267:Stilbenes / Q000494:pharmacology*; D013997:Time Factors; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D003287:Contrast Media; D011838:Radiation-Sensitizing Agents; D013267:Stilbenes; D002245:Carbon Dioxide; C011700:carbogen; C058728:fosbretabulin; D010100:Oxygen