Commercialization of targeted MRI contrast agents for prostate cancer imaging.

用于前列腺癌成像的靶向 MRI 造影剂的商业化。

• 批准号: 8979024
• 负责人: Yajuan Li
• 金额: $ 24.99万
• 依托单位: MOLECULAR THERANOSTICS, LLC
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-21 至 2017-03-20
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8979024
• 关键词: Address; Adverse effects; Affinity; Anatomy; Benign; Binding; Cessation of life; Clinical; Clinical Management; Contrast Media; Decision Making; Detection; Development; Diagnosis; Diagnostic; Diagnostic Procedure; Differential Diagnosis; Disease; Disease Progression; Dose; Early Diagnosis; Effectiveness; Erectile dysfunction; Extracellular Matrix Proteins; Goals; High Pressure Liquid Chromatography; Human; Image; Imagery; Imaging technology; Indolent; Injection of therapeutic agent; Intervention; Intestines; Ions; Lead; Lesion; Location; Magnetic Resonance Imaging; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of prostate; Measurement; Methods; Mission; Molecular; Molecular Target; Monitor; Mus; Neoplasm Metastasis; Noise; Operative Surgical Procedures; Outcome; Patients; Phase; Plasma; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Proteins; Radiation; Resolution; Risk; Screening for Prostate Cancer; Small Business Innovation Research Grant; Tissues; Tumor Cell Invasion; Tumor Tissue; Urinary Incontinence; Variant; active method; aggressive therapy; base; cancer imaging; cancer risk; cancer type; clinical decision-making; commercialization; contrast enhanced; cost; cost effective; design; emotional distress; epithelial to mesenchymal transition; gadoteridol; high risk; image guided surgery/therapy; improved; innovation; intravenous injection; men; molecular marker; mouse model; oncofetal fibronectin; phase 1 study; prostate biopsy; prostate cancer model; protein aminoacid sequence; public health relevance; screening; soft tissue; theranostics; tool; tumor

 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.

 描述（由申请人提供）：前列腺癌是一种异质性疾病，其临床结果存在显着差异，目前评估前列腺癌风险的方法结合了前列腺​​特异性抗原（PSA）筛查和随机前列腺活检，但不幸的是，该策略未能揭示病变的情况。因此，大多数患者会接受不必要的低风险前列腺癌积极治疗，以避免治疗过程中涉及手术或放射治疗，从而导致长期治疗。术语副作用，例如因此，需要采用非侵入性、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靶向 MRI 来解决这一问题。特异性针对细胞外基质 (ECM) 蛋白、癌胎纤连蛋白 (onfFN) 的造影增强剂，用于前列腺癌的早期准确检测。这些试剂还配有 Gd(III) 螯合物， MRI 是一种非侵入性临床诊断技术，可提供分辨率高达 100 µm 的整个前列腺的三维图像。最近的研究表明，细胞外蛋白的过度表达。前列腺组织内的基质蛋白与前列腺癌的侵袭性相关，该项目建议开发具有特定肽序列的 MRI 对比增强剂，然后这些靶向探针将与侵袭性结合。此外，临床医生还能够在静脉注射后患前列腺癌。 使用 MRI 可视化人类前列腺癌的位置。该 SBIR 第一阶段项目的目标是进一步优化靶向对比增强剂，并将该试剂用于临床成像前列腺癌，这是一项尚未满足的临床需求。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，它还具有非侵入性前列腺主动监测的潜力。前列腺癌的发生及及时监测疾病进展以及图像引导手术和治疗。