Multi-modality Imaging (PCa) Using Sodium MRI and PSMA PET in Men Pre-prostatectomy

The over-arching goal is to "improve the quality of life for survivors of prostate cancer" through advanced imaging tools for improved pre-treatment detection and characterization of prostate cancer through non-invasive imaging. Seminal research measuring tissue sodium concentration (TSC) in human PCa with sodium MRI has demonstrated increased TSC in prostate lesions related to tumor aggressiveness. This suggests that the addition of sodium MRI to mpMRI data will enhance the identification and characterization of prostate lesions in men with PCa. This will improve the healthcare of men through better risk stratification and treatment decisions, which will ultimately reduce overtreatment. Radio-labeled PET tracers that target PSMA have demonstrated exceptional sensitivity for molecular imaging of prostate lesions. Lesion-detection specificity of combined PSMA PET and mpMRI is very high (97 - 100%). However, PSMA PET is not practical for active surveillance of prostate cancer within the current healthcare system due to limited access and the fact that its added cost and radiation dose restricts its utility for repeated scans. However, as a tool to develop and validate our imaging assay, it is unparalleled. Compared with hybrid PET/MRI, a single modality imaging assay based only on mpMRI contrasts and endogenous TSC would be more widely available, cost effective and find wider clinical adoption - particularly for AS. The immediate expected outcome from this project is that an MRI assay combining data from mpMRI and sodium MRI will have a similar ability as PSMA PET to accurately discriminate between low- and high-risk PCa for improved treatment decisions and surveillance of low-risk disease. The transformative potential of a non-invasive, single modality, whole-gland imaging assay comprised of biomarkers from combined TSC and mpMRI could ultimately replace serial biopsies for surveillance of men with low- and intermediate-risk disease. Patients who are educated to understand the typical slow progression of low-risk PCa, surveillance methods and treatment risks are more likely to consider AS. In a systematic approach developed to improve physician counselling of low-risk PCa patients, the acceptance rate for AS was improved to 94% - a relative reduction of approximately 30% in the risk of unnecessary curative treatment. However, it is also important to note that the rate of subsequent treatment for men undergoing AS may be as high as 50% over 10 years of follow-up. The majority of these men are transitioned to treatment within 2-3 years of initial diagnosis. Identification of those men who fit the criteria for AS but are destined to have early progression is an important clinical goal. Those men can be streamed to early treatment through longitudinal assessment of lesion progression with this imaging assay and thus increase the confidence and uptake of AS protocols. AS of PCa (including possible delayed treatment) saves costs over the lifetime of a patient, compared with immediate treatment and provides superior quality of life. Research Strategy: The investigators will evaluate a non-invasive imaging assay for in vivo characterization of prostate lesions comprised of clinical multi-parametric magnetic resonance imaging (mpMRI) combined with sodium magnetic resonance imaging (sodium MRI) in a cohort of men with biopsy-proven prostate cancer. The use of mpMRI to detect, localize and stage prostate cancer is becoming standard clinical practice. Prior research in ten patients has established that tissue sodium concentration (TSC) assessed by sodium MRI increases significantly with histological grade in prostate lesions. The addition of TSC data to conventional mpMRI data (i.e. ADC values, T2 contrast, contrast agent wash-in/out rates) will be evaluated in a multivariate data analysis to demonstrate that a combination of these imaging protocols improves the characterization of PCa. The resulting predictive tool (imaging assay) will accurately discriminate between low- and high-risk PCa for improved treatment decisions and to assess possible progression of low-risk disease during surveillance. This imaging assay will be validated against positron emission tomography (PET) using a radio-labeled tracer which binds to prostate-specific membrane antigen (PSMA). PSMA PET is arguably the most sensitive imaging method for detection of intra-prostatic lesions. Importantly, it has a high sensitivity for prostate lesion detection (\>90%), even for lower tumor grades where mpMRI has difficulties. Maximum standard uptake value (SUVmax) of this radiotracer has been positively correlated with Gleason grade and as such, is an excellent comparator for TSC assessment of lesion aggressiveness. Unfortunately, the limited accessibility and cost of PET hinders its clinical application. In this project, the investigators expect to validate that the addition of sodium MRI to mpMRI can provide similar lesion characterization compared to PSMA PET. Data supporting this hypothesis will be acquired using a hybrid PET/MRI system because this is the best imaging platform for this project. If successful, the incorporation of sodium MRI into existing mpMRI protocols would improve characterization of disease and be a more cost effective and generalizable innovation compared to PET-based techniques that require both an expensive probe as well as hybrid imaging platforms.