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.