Abstract Prostate cancer is a highly heterogeneous disease and the second most cause of cancer death of men in the USA. 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 invasive and non-invasive prostate cancers. As a result, most patients will receive unnecessary active treatment for low-risk prostate cancer. Thus, development of non- invasive and accurate diagnostic imaging technology to localize and differentiate high-risk prostate cancer offers a new tool to assist physicians in risk-stratification and decision-making, and to spare millions of patients with low-risk cancer from unnecessary aggressive treatment. The mission of Molecular 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, and none in normal tissues. The ultimate goal of this project is to commercialize a targeted contrast agent, MT218, for accurate early detection, localization, and differential diagnosis of high-risk prostate cancer with MRI. We have optimized and identified a lead targeted MRI contrast agent, proven it effective in various animal in vivo tumor models, and completed the chemistry, manufacturing and control (CMC) work for the preclinical batches. Moreover, we demonstrated the GLP preclinical safety of MT218 according to the FDA’s guidelines for an IND submission. MT218 has shown rapid and complete clearance via renal excretion, with no detectable brain retention, and low pharmacological risk and toxicity in rats and dogs. An IND was approved by the FDA in March 2021 for phase 1 clinical trial in Ohio. The first two dosing cohorts have shown no adverse effects and rapid excretion from the body as the clinical contrast agents. The proposed work in this SBIR project will allow the company to carry out the proof-of-concept phase 2a clinical trial in the patents with confirmed high-risk prostate cancer. The specific aims are 1) to perform open-label phase 2a clinical trial to investigate initial imaging efficacy of MT218 in diagnostics MRI in PCa patients; 2) to develop a liquid phase synthetic procedure for scale-up cGMP production. Successful development of our imaging technology has the potential to accurately detect, localize, and diagnose prostate cancer with MRI’s < 1 mm spatial resolution, reduce the use of invasive prostate biopsy, and so improve decision-making in clinical management of prostate cancer. It also has the potential for accurate non-invasive Active Surveillance of prostate cancer and timely monitoring of disease progression, as well as image-guided focal therapy. C...