title: Diffusion-weighted magnetic resonance imaging allows noninvasive in vivo monitoring of the effects of combretastatin a-4 phosphate after repeated administration.
abstract: The noninvasive assessment of anticancer treatment efficacy is very important for the improvement of therapeutic window. The purpose of the present study was to evaluate the antitumoral effects of the vascular targeting agent, combretastatin A-4 phosphate (CA-4-P), at selected time points after repeated intraperitoneal drug administrations (25 mg/kg), using diffusion-weighted magnetic resonance imaging (DW-MRI). The experiments were performed during an overall follow-up period of 3 weeks on WAG/Rij rats with subcutaneously growing rhabdomyosarcomas. Each animal served as its own baseline. The DW-MRI studies were quantified by calculating the apparent diffusion coefficient (ADC) for different low and high b-values to separate the effects on tumor vasculature and cellular integrity. The changes in ADC as well as the extent of necrosis development (proportional to the tumor volume), measured on the MR images, were of comparable magnitude after each treatment. All ADC values showed a significant decrease at 6 hours, followed by a significant increase at 2 days for various CA-4-P administrations. DW-MRI allowed us to monitor both reduction in perfusion and changes in the extent of tumor necrosis after CA-4-P injection. Repeated CA-4-P administration retains efficacy in rat rhabdomyosarcomas, with similar findings after each drug administration.
authors.affiliation: Department of Radiology, University Hospitals Leuven, Herestraat 49, Leuven B-3000, Belgium.
authors.forename: Harriet C
authors.initials: HC
authors.lastname: Thoeny
authors.forename: Frederik
authors.initials: F
authors.lastname: De Keyzer
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.forename: Vincent
authors.initials: V
authors.lastname: Vandecaveye
authors.forename: Erik K
authors.initials: EK
authors.lastname: Verbeken
authors.forename: Bisan
authors.initials: B
authors.lastname: Ahmed
authors.forename: Xihe
authors.initials: X
authors.lastname: Sun
authors.forename: Yicheng
authors.initials: Y
authors.lastname: Ni
authors.forename: Hilde
authors.initials: H
authors.lastname: Bosmans
authors.forename: Robert
authors.initials: R
authors.lastname: Hermans
authors.forename: Allan
authors.initials: A
authors.lastname: van Oosterom
authors.forename: Guy
authors.initials: G
authors.lastname: Marchal
authors.forename: Willy
authors.initials: W
authors.lastname: Landuyt
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000627:therapeutic use*; D038524:Diffusion Magnetic Resonance Imaging; D007274:Injections, Intraperitoneal; D008297:Male; D009368:Neoplasm Transplantation; D051381:Rats; D011919:Rats, Inbred Strains; D012208:Rhabdomyosarcoma / Q000188:drug therapy* / Q000473:pathology; D013267:Stilbenes / Q000008:administration & dosage / Q000627:therapeutic use*; D047368:Tumor Burden
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D013267:Stilbenes; C058728:fosbretabulin