title: Contrast-enhanced MR imaging assessment of tumor capillary permeability: effect of irradiation on delivery of chemotherapy.
abstract: OBJECTIVE
  To assess the effect of x rays on tumor capillary permeability with macromolecular contrast medium (MMCM)-enhanced magnetic resonance (MR) imaging.
  
  
  METHODS
  One of paired R3230 mammary adenocarcinomas implanted in the flanks of 48 Fischer rats was treated with a single 5- or 15-Gy dose of x rays. After 1 or 3 days, MR imaging in 30 rats was performed unenhanced and enhanced with albumin-(gadolinium diethylenetriaminepentaacetic acid)30 (0.02 mmol gadolinium per kilogram body weight). Signal intensity enhancement was analyzed to estimate fractional blood volume and permeability-surface area product (PS). In 18 irradiated rats, 2.5 mg/kg cisplatin was injected intravenously, and fractional tumor platinum concentrations were measured spectrometrically.
  
  
  RESULTS
  MR imaging showed highest capillary permeability 1 day after 15 Gy (PS 110% above control [P<.001]); PS was elevated 57% 1 day after 5 Gy and 63% 3 days after 15 Gy (P<.05). The largest mean tumor platinum fraction occurred 1 day after 15 Gy: 48% versus 20% (control)(P<.05).
  
  
  CONCLUSIONS
  Transient irradiation-induced increase in tumor capillary permeability to cisplatin can be quantified with MMCM-enhanced MR imaging.
authors.affiliation: Department of Radiology, University of California, San Francisco 94143, USA.
authors.forename: H C
authors.initials: HC
authors.lastname: Schwickert
authors.forename: M
authors.initials: M
authors.lastname: Stiskal
authors.forename: T P
authors.initials: TP
authors.lastname: Roberts
authors.forename: C F
authors.initials: CF
authors.lastname: van Dijke
authors.forename: J
authors.initials: J
authors.lastname: Mann
authors.forename: A
authors.initials: A
authors.lastname: Mühler
authors.forename: D M
authors.initials: DM
authors.lastname: Shames
authors.forename: F
authors.initials: F
authors.lastname: Demsar
authors.forename: A
authors.initials: A
authors.lastname: Disston
authors.forename: R C
authors.initials: RC
authors.lastname: Brasch
mesh_terms: D000418:Albumins; D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002199:Capillary Permeability / Q000528:radiation effects*; D002945:Cisplatin / Q000493:pharmacokinetics* / Q000627:therapeutic use; D003287:Contrast Media; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005682:Gadolinium; D019786:Gadolinium DTPA; D046911:Macromolecular Substances; D008279:Magnetic Resonance Imaging; D008325:Mammary Neoplasms, Experimental / Q000098:blood supply* / Q000188:drug therapy / Q000532:radiotherapy*; D009942:Organometallic Compounds; D004369:Pentetic Acid / Q000031:analogs & derivatives*; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D000418:Albumins; D000970:Antineoplastic Agents; D003287:Contrast Media; D046911:Macromolecular Substances; D009942:Organometallic Compounds; C058946:albumin-(gadolinium-DTPA); D004369:Pentetic Acid; D005682:Gadolinium; D019786:Gadolinium DTPA; D002945:Cisplatin