title: Dynamic contrast-enhanced MRI for assessing therapeutic response of choroidal neovascularization in a rat model.
abstract: OBJECTIVE
  We evaluated the potential of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) as a noninvasive biomarker of choroidal neovascularization (CNV) and its utility as a tool for monitoring therapeutic response in laser-induced rat CNV models.
  
  
  METHODS
  CNV was induced in the right eyes of 14 rats using a laser. Rats (n = 7) were treated daily for 14 days with a candidate drug (KR-31831, 50 mg/kg of body weight) having antiangiogenic effects, whereas control rats (n = 7) were treated with the vehicle alone (10% cremophor, 10% absolute ethyl alcohol, and 80% saline). DCE-MRI examinations were performed on the day before surgery (D - 1), and 3, 7, and 14 days after surgery (D + 3, D + 7, and D + 14), from which pharmacokinetic parameters (K(trans), v(e), v(p)) were calculated. Angiography was performed to visualize CNV using FITC-labeled high molecular weight dextran after MRI on D + 14. The paired Wilcoxon test and Mann-Whitney U test were performed for statistical analysis.
  
  
  RESULTS
  The K(trans) and v(e) values of the CNV-induced right eyes were significantly higher than those of the intact eyes in control rats at D + 14 (P < 0.05). In the CNV-induced eyes, the relative K(trans) and v(e) values of the KR-31831-treated group were significantly lower than those of the nontreated group at D + 14 (P < 0.05). The angiography showed that decreased CNV was observed in rats treated with KR-31831.
  
  
  CONCLUSIONS
  Quantitative DCE-MRI produces noninvasive biomarker of CNV, thus allowing monitoring of therapeutic response of antiangiogenic drugs in neovascular age-related macular degeneration (AMD).
authors.affiliation: Department of Radiology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jae-Hun
authors.initials: JH
authors.lastname: Kim
authors.forename: Geun Ho
authors.initials: GH
authors.lastname: Im
authors.forename: Jaemoon
authors.initials: J
authors.lastname: Yoon
authors.forename: Jehoon
authors.initials: J
authors.lastname: Yang
authors.forename: Julius Juhyun
authors.initials: JJ
authors.lastname: Chung
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Cha
authors.forename: Sun I
authors.initials: SI
authors.lastname: Kim
authors.forename: Don-il
authors.initials: DI
authors.lastname: Ham
authors.forename: Jung
authors.initials: J
authors.lastname: Hee Lee
mesh_terms: D000818:Animals; D001578:Benzopyrans / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002829:Choroid / Q000187:drug effects / Q000473:pathology*; D020256:Choroidal Neovascularization / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism; D004195:Disease Models, Animal; D007093:Imidazoles / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051381:Rats; D016896:Treatment Outcome
chemical_list: D001578:Benzopyrans; D007093:Imidazoles; C503693:KR 31831