title: Pharmacokinetic parameters as a potential predictor of response to pharmacotherapy in benign prostatic hyperplasia: a preclinical trial using dynamic contrast-enhanced MRI.
abstract: We sought to assess the possibility of using pharmacokinetic parameters as a predictor of response to benign prostatic hyperplasia (BPH) pharmacotherapy via a randomized, placebo-controlled, animal preclinical trial using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Twelve male beagles with BPH were enrolled in a preclinical experimental drug trial and divided into two randomized groups with six beagles each: one drug (finasteride) group and one placebo (control) group. Two baseline MRI examinations and three follow-ups during treatment were performed on a clinical 1.5-T MRI system using axial T1- and T2-weighted magnetic resonance images for prostate volume measurement and DCE-MRI for the assessment of prostate microcirculation. A total of 0.2 mmol/kg body weight of the Gd-based contrast agent was administered with an injection rate of 0.2 ml/s. The pharmacokinetic parameters, maximum enhancement ratio (MER), transfer constant and rate constant, were assessed to characterize the microcirculation in the parenchymal zone. The time-signal intensity curve from the external iliac artery was used as the arterial input function. The correlation between baseline evaluations (prostate volume and pharmacokinetic parameters) and therapy-induced prostate volume changes under finasteride treatment were assessed. The changes in prostate volume at the end of the trial exhibited a significant linear correlation to the initial parenchymal MER (P < .02) in the finasteride group. Larger prostate volume reductions coincided with smaller initial parenchymal MER. These findings show considerable promise of using parenchymal MER as a predictor of response to BPH pharmacotherapy with finasteride.
authors.affiliation: Department of Radiology, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Guang
authors.initials: G
authors.lastname: Jia
authors.forename: Johannes T
authors.initials: JT
authors.lastname: Heverhagen
authors.forename: Hannes
authors.initials: H
authors.lastname: Henry
authors.forename: Hans
authors.initials: H
authors.lastname: Polzer
authors.forename: Klaus T
authors.initials: KT
authors.lastname: Baudendistel
authors.forename: Hendrik
authors.initials: H
authors.lastname: von Tengg-Kobligk
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Levine
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Rosol
authors.forename: Michael V
authors.initials: MV
authors.lastname: Knopp
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000493:pharmacokinetics*; D004195:Disease Models, Animal; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D018120:Finasteride / Q000494:pharmacology*; D005682:Gadolinium; D006571:Heterocyclic Compounds / Q000493:pharmacokinetics*; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008833:Microcirculation; D009942:Organometallic Compounds / Q000493:pharmacokinetics*; D011446:Prospective Studies; D011467:Prostate / Q000098:blood supply; D011470:Prostatic Hyperplasia / Q000188:drug therapy* / Q000473:pathology; D011897:Random Allocation; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
chemical_list: D003287:Contrast Media; D004791:Enzyme Inhibitors; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; C062402:gadoteridol; D018120:Finasteride; D005682:Gadolinium