INVESTIGATIVE UROLOGY

Dynamic Contrast Enhanced Magnetic Resonance Imaging as a Biological Marker to Noninvasively Assess the effect of Finasteride on Prostatic Suburethral Microcirculation
Jia G, Heverhagen JT, Polzer H, Jacko RV, Liang J, Zhang J, Levine AL, Rosol TJ, Knopp MV
Department of Radiology, Ohio State University, Columbus, Ohio, USA
J Urol. 2006; 176: 2299-304

• Purpose: We assessed dynamic contrast enhanced magnetic resonance imaging as a biological marker of in vivo changes in microcirculation in the prostatic suburethral region.
• Materials and Methods: A total of 12 male beagle dogs with spontaneous benign prostatic hyperplasia were randomly allocated to 1 control group and 1 finasteride (Merck and Co., Whitehouse Station, New Jersey) treated group. Two baseline dynamic contrast enhanced magnetic resonance imaging examinations and 3 followups were performed to assess prostate microcirculation. Treatment duration was 3 months. The pharmacokinetic parameters evaluated in prostatic suburethral areas were the maximum enhancement ratio in AU, time to maximum signal enhancement in minutes, amplitude in AU and the exchange rate constant in minutes(-1).
• Results: After completion of the therapeutic regimen time to maximum signal enhancement was significantly longer in the finasteride group than in controls (p < 0.01). Amplitude and the exchange rate constant decreased 39% and 34%, respectively, in the finasteride group at the end of treatment, which significantly differed from results in the control group (p < 0.05).
• Conclusions: Dynamic contrast enhanced magnetic resonance imaging is capable of noninvasively assessing the prostatic microcirculation changes induced by finasteride. Pharmacokinetic parameters show considerable promise to be biomarkers for the development of benign prostatic hyperplasia drugs such as 5alpha-reductase inhibitors by the in vivo monitoring of microvascular changes. A relevant clinical application could be the pretreatment assessment of finasteride effectiveness to decrease perioperative bleeding at transurethral prostate resection and in treatment for hematuria.
  
  
• Editorial Comment
  During the last years we learned that finasteride could decrease prostatic bleeding, both in benign prostatic hyperplasia (BPH) and in transurethral resection of the prostate (TURP), and we have been using finasteride in the clinical setting for these proposes. Nevertheless, the mechanism of finasteride action in stopping bleeding is still unknown.
  The authors of the present paper used male beagle dogs to assess dynamic contrast enhanced magnetic resonance imaging as a biological marker of in vivo changes in microcirculation in the prostatic suburethral region. They found that subjects in the finasteride group had decreased microcirculation, as expressed by lower and slower contrast enhancement, and as quantified by increased Tmax, and decreased A and kep in the prostatic suburethral area. They concluded that finasteride would decrease the prostatic microcirculation and therefore diminish prostatic bleeding in BPH and TURP.
  In a recent experimental paper, Canda et al. (1) evaluated the effects of finasteride on the vascular surface density (VSD), number of microvessels (NVES) and vascular endothelial growth factor (VEGF) expression of the rat prostate. After studying 19 adult rats, the authors found that the mean prostatic weights were decreased significantly in rats given finasteride (p=0.0001). On the other hand, finasteride does not seem to decrease VSD, NVES and VEGF expression at the level of the rat prostate. The effect of reduction of bleeding in BPH is more likely to be due to its effect on shrinking glandular hyperplasia, which might enhance vessel wall stability, rather than decreasing overall vascularity (1).
  From these two papers, we can infer that the exact mechanism of action of finasteride on the prostatic vessels is still open to research and discussion.

Reference
1. Canda AE, Mungan MU, Yilmaz O, Yorukoglu K, Tuzel E, Kirkali Z: Effects of finasteride on the vascular surface density, number of microvessels and vascular endothelial growth factor expression of the rat prostate. Int Urol Nephrol. 2006; 38: 275-80.

Dr. Francisco Sampaio
Full-Professor and Chair, Urogenital Research Unit
State University of Rio de Janeiro
Rio de Janeiro, Brazil