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

用于前列腺癌鉴别诊断的 MRI 造影剂的商业化。

• 批准号: 9534548
• 负责人: Yajuan Li
• 金额: $ 99.97万
• 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 2021-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9534548
• 关键词: Adverse effects; Affinity; Aggressive behavior; Animal Model; Appearance; Binding; Biodistribution; Biopsy; Blood Screening; Cancer Etiology; Carcinoma; Cells; Cessation of life; Clinical; Clinical Data; Clinical Management; Clinical Trials; Contrast Media; Data; Decision Making; Detection; Development; Diagnosis; Diagnostic Imaging; Diagnostic Procedure; Differential Diagnosis; Disease; Disease Progression; Dose; Drug Kinetics; Early Diagnosis; Effectiveness; Erectile dysfunction; Extracellular Matrix; FDA approved; Formulation; Freeze Drying; Goals; Hour; Human; Imagery; Imaging Techniques; Imaging technology; Indolent; Intestines; Lead; Lesion; Lethal Dose 50; Location; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of prostate; Metabolic Clearance Rate; Methods; Mission; Modeling; Molecular; Molecular Target; Monitor; Mus; Neoplasm Metastasis; No-Observed-Adverse-Effect Level; Noise; Normal tissue morphology; Oncoproteins; Operative Surgical Procedures; Osmolalities; PC3 cell line; Patients; Pharmacology; Phase; Physicians; Plasma; Production; Prohance; Prostate; Prostate Cancer therapy; Prostate-Specific Antigen; Prostatic Neoplasms; Proteins; Radiation; Rattus; Renal clearance function; Residual state; Risk; Risk stratification; Rodent; Safety; Screening for Prostate Cancer; Sensitivity and Specificity; Small Business Innovation Research Grant; Structure; Temperature; Testing; Time; Tissues; Toxic effect; Ultrasonography; Urinary Incontinence; Urologist; Water; Xenograft procedure; active method; angiogenesis; aqueous; base; cancer cell; cancer imaging; cancer risk; clinical diagnostics; clinical imaging; clinical translation; commercialization; contrast enhanced; cost effective; epithelial to mesenchymal transition; high resolution imaging; high risk; image guided therapy; imaging agent; imaging approach; improved; innovation; men; molecular imaging; mortality; novel; overexpression; preclinical study; prevent; procedure cost; prostate biopsy; prostate cancer risk; reconstitution; safety study; scale up; screening; stemness; theranostics; therapy outcome; tool; tumor

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.

摘要 前列腺癌是一种高度异质性的疾病，并且是癌症死亡的第二大原因。 男人在美国。目前评估前列腺癌风险的方法结合了联合收割机前列腺特异性抗原（PSA） 筛查和随机前列腺活检。不幸的是，这种策略无法揭示病变的位置， 不能准确区分侵袭性和非侵袭性前列腺癌。因此，在本发明中， 大多数患者将接受不必要的低风险前列腺癌积极治疗，以避免 正在接受治疗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，非侵入性和 准确的诊断成像技术，以定位和区分高危前列腺癌提供了一个新的 帮助医生进行风险分层和决策的工具， 不必要的积极治疗会导致癌症。 分子治疗学的使命（fka前列腺治疗学）是将一种新的 一种靶向与上皮间质相关的癌蛋白的分子成像方法 转化（EMT）、癌细胞干细胞性、血管生成、增殖和转移。癌蛋白具有 在高危前列腺癌的肿瘤细胞外基质中高表达，在低级别肿瘤中低表达， 正常组织中无。该项目的目标是将安全有效的靶向造影剂商业化 用于准确早期检测、定位和鉴别诊断高危前列腺癌的试剂， 核磁共振在第一阶段，我们已经优化并确定了一种用于临床的主要靶向MRI造影剂， 翻译.该项目第一阶段的所有里程碑都已实现。代理拥有 在高危前列腺癌中，而不是在缓慢生长的前列腺癌中，稳健的特异性对比增强的上级能力 在动物模型中的低风险肿瘤，并有可能可视化和区分高风险前列腺 癌症MRI SBIR第II阶段的目标是开发造影剂的主要配方， 进行FDA要求的eIND使能研究，并将用于前列腺临床成像的药物商业化 癌具体目标是：1）按比例扩大靶向造影剂的合成，并开发一种靶向造影剂。 临床前研究和临床试验的主导产品配方; 2）验证 用于在临床MRI扫描仪上进行前列腺癌成像的制剂，并确定其最低有效性 剂量; 3）在啮齿动物中进行eIND使能药代动力学和安全性研究。无创精确 前列腺癌的检测是前列腺癌管理的未满足的临床需求。临床试验将 一旦eIND获得FDA批准，就立即启动。成功开发我们的成像技术 技术有可能准确地检测，定位和诊断前列腺癌，取代 侵入性前列腺活组织检查和改善前列腺癌临床管理决策。它还 具有非侵入性主动监测前列腺癌和及时监测疾病的潜力 进展以及图像引导治疗。