Prostate cancer is a heterogeneous disease with significant variations in its clinical outcome. 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. Therefore, non-invasive and accurate diagnostic methods to determine the location of prostate cancer and to assess its immediate risk are needed. The mission of Prostate Theranostics is to address this problem by developing targeting MRI contrast enhancing agents specific to an extracellular matrix (ECM) protein, oncofetal fibronectin (onfFN), for early accurate detection of prostate cancer. These agents would also be fitted with Gd(III)-chelates that would allow their location to be visualized within men's prostates using MRI. MRI is a non-invasive clinical diagnostic technique and can provide three-dimensional images of whole prostate with a resolution as high as 100 m. Recent studies show that the over expression of extracellular matrix proteins within prostate tissue are correlated to prostate cancer aggressiveness. In addition, these proteins can be targeted using specific peptide sequences. This project proposes to develop MRI contrast-enhancing agents with specific peptide sequences. These targeting probes would then bind to aggressive prostate cancer after intravenous injection. In addition, the clinician would be able to visualize location of human prostate cancer using MRI. The objectives of this SBIR Phase I project are to further optimize the targeted contrast-enhancing agent and commercialize the agent for clinical imaging prostate cancer. Non-invasive accurate detection of prostate cancer is an unmet clinical need for prostate cancer management. Successful development of our imaging technology has the potential to accurately detect 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 surgery and therapy.
Although the detection of prostate cancer is critical, clinicians still need to know where the cancer is located and-most importantly-if the cancer is aggressive. The development of onfFN targeting Gd(III)-chelates offer an innovative approach to the non-invasive differentiation and visualization of prostate cancer.
|Han, Zheng; Li, Yajuan; Roelle, Sarah et al. (2017) Targeted Contrast Agent Specific to an Oncoprotein in Tumor Microenvironment with the Potential for Detection and Risk Stratification of Prostate Cancer with MRI. Bioconjug Chem 28:1031-1040|