Gadoxetate Sodium Enhanced MRI as a Biomarker for Aggressive Prostate Cancer

A substantial body of evidence implicates androgen hormones, such as testosterone, play a key role in aggressive prostate carcinogenesis, and much work has been done to evaluate the relationship between the concentration of testosterone and clinical outcome of patients with prostate cancer. Several uptake transporters localized to the cell membrane have shown to enhance steroid hormone uptake, and these same transporters are also expressed within the prostate where they could increase the capability of neoplastic cells to use testosterone. One group of uptake carriers is the organic anion-transporting polypeptide (OATP) superfamily encoded by SLCO genes. OATPs are localized to normal human hepatocytes. OATP1B3, a member of this family, is also expressed by cancer cells derived from aggressive prostate cancer. Studies have shown that in prostate cancer, testosterone uptake by cells occurs via OATP1B3, and its presence increases from undetectable levels in normal prostatic tissue and benign hyperplasia to marked expression in aggressive prostate cancer. Current prostate cancer (PCa) diagnosis methods have false positives and are limited in predicting cancer recurrence. Gadoxetate Sodium is a magnetic resonance imaging agent which is FDA-approved gadolinium chelate for detecting hepatocellular carcinoma, as normal hepatocytes express OATP1B3 while most hepatocellular carcinomas do not. Gadoxetate Sodium acts as a substrate for OTAP1B3, therefore, OATP1B3 positive prostate tumors can potentially be visualized on MR imaging. Making this contrast agent useful in the evaluation of OATP1B3 status in patients with aggressive PCa and potentially serve as a prognostic and treatment biomarker. The investigators hypothesize that Gadoxetate Sodium -enhanced MRI can differentiate aggressive PCa and predict its early recurrence. The investigators aim to enroll 50 patients and sort them into localized or metastatic PCa, based on tumor grade. Subjects that agree to participate will be scheduled for a research pelvic MRI with the Gadoxetate Sodium contrast within 3 weeks of their office visit. The procedure is be conducted as a standard pelvic MRI but instead of gadolinium contrast being administered, Gadoextate Sodium will be dosed at 0.1/mL per kilogram of body weight (as prescribed on the contrast label). Once the subject has undergone the research MRI scan using Gadoxetate Sodium, the MRI and assigned enhancement ratios will be reviewed. Contrast enhancement ratios (CERs) will be calculated to evaluate the difference in the degree of enhancement between the tumors and normal tissue. Subject demographic information, medical history and enhancement ratios will be recorded in the study database. Previously obtained remnant biopsy samples from enrolled subjects will be used for transcriptome and epigenome profiling using genome-wide and targeted gene approaches.