Commercialization of an MRI contrast agent for differential diagnosis of prostate cancer.

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Abstract Prostate cancer is a highly heterogeneous disease and the second most cause of cancer death of men in the US. Current methods to assess prostate cancer risk combine prostate specific antigen (PSA) screening and random prostate biopsy. Unfortunately, this strategy fails to reveal the lesion’s location and does not accurately differentiate between aggressive and non-aggressive prostate cancers. As a result, most patients will receive unnecessary active treatment for low-risk prostate cancer in order to avoid under treatment. Active treatment involves surgery or radiation, often causing long-term side effects such as urinary incontinence, erectile dysfunction, or bowel urgency. Thus, development of non-invasive and accurate diagnostic imaging technology to localize and differentiate high-risk prostate cancer offer a new tool to assist physicians in risk-stratification and decision making and to spare millions patients with low- risk cancer from unnecessary aggressive treatment. The mission of Molecular Theranostics (fka Prostate Theranostics) is to commercialize a novel molecular imaging approach that targets an oncoprotein associated with epithelial-to-mesenchymal transition (EMT), cancer cell stemness, angiogenesis, proliferation, and metastasis. The oncoprotein has a high expression in the tumor extracellular matrix of high-risk prostate cancer, low in low-grade tumor, none in normal tissues. The goal of this project is to commercialize a safe and effective targeted contrast agent for accurate early detection, localization, and differential diagnosis of high-risk prostate cancer with MRI. In phase I, we have optimized and identified a lead targeted MRI contrast agent for clinical translation. All of the milestones in Phase I of the project have been achieved. The agent possesses the superior ability of robust specific contrast enhancement in high-risk prostate cancer, not in slow growing low-risk tumors in animal models, and has the potential to visualize and differentiate high-risk prostate cancers with MRI. The objectives of this SBIR Phase II are to develop a lead formulation of the contrast agent, to perform FDA required eIND enabling studies, and to commercialize the agent for clinical imaging prostate cancer. The specific aims are 1) to scale up the synthesis of the targeted contrast agent and develop a lead product formulation for pre-clinical study and clinical trials; 2) to validate the effectiveness of the formulation for prostate cancer imaging on a clinical MRI scanner and to determine its minimally effective dose; 3) to perform eIND-enabling pharmacokinetics and safety studies in rodents. Non-invasive accurate detection of prostate cancer is an unmet clinical need for prostate cancer management. Clinical trials will be initiated as soon as the eIND is approved by the FDA. Successful development of our imaging technology has the potential to accurately detect, localize, and diagnose prostate cancer, replace invasive prostate biopsy, and improve decision-making in clinical management of prostate cancer. It also has the potential for non-invasive active surveillance of prostate cancer and timely monitoring of disease progression, as well as image-guided therapy.