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。

基本信息

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
项目类别：
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

项目摘要

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.

抽象的前列腺癌是一种高度异质性的疾病，是导致癌症死亡的第二大原因。美国男性目前评估前列腺癌风险的方法是结合前列腺特异性抗原（PSA）。不幸的是，这种策略未能揭示病变的位置和情况。不能准确区分侵袭性和非侵袭性前列腺癌。大多数患者会接受不必要的低风险前列腺癌积极治疗，以避免积极治疗包括手术或放射治疗，通常会导致长期副作用，例如如尿失禁、勃起功能障碍或肠急迫，因此，开发了非侵入性和非侵入性的治疗方法。准确的诊断成像技术可定位和区分高危前列腺癌，提供了新的方法帮助医生进行风险分层和决策的工具，并让数百万低危患者免受伤害因不必要的积极治疗而导致癌症的风险。分子治疗诊断学（又名前列腺治疗诊断学）的使命是将小说商业化针对与上皮间质相关的癌蛋白的分子成像方法转变（EMT）、癌细胞干性、血管生成、增殖和转移。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，该项目的目标是将安全且有效的靶向对比剂商业化。用于高危前列腺癌的准确早期检测、定位和鉴别诊断的试剂在第一阶段，我们优化并确定了一种用于临床的领先靶向 MRI 造影剂。该项目第一阶段的所有里程碑均已实现。对高风险前列腺癌（而非缓慢生长的前列腺癌）具有强大的特异性对比增强的卓越能力动物模型中的低风险肿瘤，并具有可视化和区分高风险前列腺的潜力通过 MRI 检查癌症。 SBIR 第二阶段的目标是开发造影剂的先导配方，执行 FDA 要求的 eIND 支持研究，并将用于前列腺临床成像的试剂商业化具体目标是 1) 扩大靶向造影剂的合成并开发一种临床前研究和临床试验的主导产品配方；2) 验证产品的有效性在临床 MRI 扫描仪上进行前列腺癌成像的配方并确定其最低效果剂量；3) 在啮齿类动物中进行支持 eIND 的药代动力学和安全性研究。癌症检测是前列腺癌治疗的一个未满足的临床需求。一旦 eIND 获得 FDA 批准，我们的成像技术的成功开发就会启动。技术有潜力准确检测、定位和诊断前列腺癌，替代侵入性前列腺活检，并改善前列腺癌临床管理的决策。具有对前列腺癌进行非侵入性主动监测并及时监测疾病的潜力进展以及图像引导治疗。