The main goal of this study is to develop a noninvasive technique to predict the precise volume of epithelial vs. stromal contents in individual patients with prostatic hyperplasia (BPH) because this will provide the best strategy for selection of patients for medical therapy. The rationale far this proposal is that prior studies from our laboratory have shown that in vivo citrate concentration measured by endorectal Magnetic Resonance Spectroscopy (MRS) is associated with epithelial tissues in BPH and is absent in stromal cells. The hypothesis of this proposal is that citrate concentration per unit volume of BFH measured by MRS can provide a means of noninvasively measuring epithelial cell volume and that pretreatment or early (4 weeks) post-treatment citrate levels after androgen suppression will predict degree of relief likely to obtained after therapy. This hypothesis will be tested in experiments with the following specific aims:
In Specific Aim 1 citrate densities (citrate concentration per unit volume of tissue) will be measured in 45 patients who will undergo radical prostatectomy for small stage B (T1) prostate cancer not involving the transition (BPH) zone of the prostate. Citrate densities will be measured by single voxel and 3 dimensional spectroscopy, confirmed by tissue extract studies (n=15) and correlated to volume of epithelial cells on step section histology of surgically removed glands (n=30).
In Specific Aims 2 & 3 changes in citrate density before and after 1 month and 3 months of androgen suppression (using Leuprolide acetate) will be correlated to degree of objective relief of obstruction by multichannel urodynamic studies. 75 patients with symptomatic BPH and small prostate cancers (not involving the BPH zone) will undergo 3 months of androgen suppression followed by surgery. MRS measured citrate changes after androgen suppression will be confirmed by biochemical assays of excised tissues (n=15) and decrease in citrate density will be correlated to findings of epithelial atrophy on step section histopathology of excised glands (n=60). This study is important because BFH requiring treatment will affect 30% of all men. Androgen suppression is a major therapy for BPH is expensive ($200-500/month) and currently there is no way to select patients who may specifically benefit from therapy. Endorectal MRS provides a unique means to study cellular metabolism after androgen suppression and may help in design and evaluation of potential new agents for BPH treatment.
| Kim, Hee-Won; Buckley, David L; Peterson, David M et al. (2003) In vivo prostate magnetic resonance imaging and magnetic resonance spectroscopy at 3 Tesla using a transceive pelvic phased array coil: preliminary results. Invest Radiol 38:443-51 |
