Commercialization of targeted MRI contrast agents for prostate cancer imaging.

 描述（由申请人提供）：前列腺癌是一种异质性疾病，其临床结局存在显著差异。目前评估前列腺癌风险的方法将联合收割机前列腺特异性抗原（PSA）筛查和随机前列腺活检结合起来。不幸的是，这种策略未能揭示病变的位置，并且不能准确区分侵袭性和非侵袭性前列腺癌。因此，大多数患者将接受不必要的积极治疗，以避免治疗不足。积极的治疗包括手术或放射治疗，通常会引起长期的副作用，如尿失禁，勃起功能障碍或肠紧迫。因此，需要非侵入性和准确的诊断方法来确定前列腺癌的位置并评估其直接风险。 前列腺治疗诊断学的使命是通过开发特异于细胞外基质（ECM）蛋白、癌胚纤维连接蛋白（onfFN）的靶向MRI造影增强剂来解决这一问题，以早期准确检测前列腺癌。这些药物还将配备Gd（III）螯合物，这将使它们在男性前列腺中的位置可以使用MRI可视化。MRI是一种非侵入性临床诊断技术，可以提供分辨率高达100 µm的整个前列腺的三维图像。最近的研究表明，前列腺组织中细胞外基质蛋白的过度表达与前列腺癌的侵袭性相关。此外，这些蛋白质可以使用特定的肽序列靶向。本计画拟开发具特定胜肽序列之磁振造影剂。这些靶向探针在静脉注射后将与侵袭性前列腺癌结合。此外，临床医生将能够 使用MRI可视化人类前列腺癌的位置。 该SBIR I期项目的目标是进一步优化靶向对比增强剂，并将其商业化用于前列腺癌的临床成像。前列腺癌的非侵入性准确检测是前列腺癌管理的未满足的临床需求。我们的成像技术的成功开发有可能准确地检测和诊断前列腺癌，取代侵入性前列腺活检，并改善前列腺癌临床管理的决策。它还具有对前列腺癌进行非侵入性主动监测和及时监测疾病进展以及图像引导手术和治疗的潜力。

 DESCRIPTION (provided by applicant): 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 µm. 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.