Targeted MRI contrast agents for differential diagnosis of prostate cancer

靶向 MRI 造影剂用于前列腺癌的鉴别诊断

基本信息

批准号：
9903251
负责人：
ZHENG-RONG LU
金额：
$ 42.62万
依托单位：
CASE WESTERN RESERVE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-04-01 至 2022-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9903251
关键词：
Animal Model Animals Binding Biological Biopsy Caliber Cancer Biology Cancer Etiology Cancer Patient Carcinoma Cessation of life Chelating Agents Clinic Clinical Clinical Data Clinical Management Contrast Media Detection Development Diagnosis Diagnostic Imaging Diagnostic Procedure Differential Diagnosis Disease Disease Management Drug Kinetics Early Diagnosis Economics Effectiveness Event Excretory function Extracellular Matrix Fibronectins Goals Human Imaging Device Imaging Techniques Imaging technology Indolent Intervention Lead Magnetic Resonance Imaging Malignant neoplasm of prostate Medical Micrometastasis Modeling Molecular Mus Neoplasm Metastasis Normal tissue morphology Oncology Oncoproteins PSA screening Pathology Patient Care Patients Peptides Physicians Physics Physiological Positron-Emission Tomography Prostate Prostate Cancer therapy Prostatic Neoplasms Research Resolution Risk Risk stratification Safety Screening procedure Signal Transduction Specimen Testing Time Tissues Toxic effect Tumor Tissue Tumor-Derived Ultrasonography Universities Visualization aggressive therapy angiogenesis cancer cell chelation clinical application clinical development clinical practice clinical translation contrast enhanced cost effective efficacy testing epithelial to mesenchymal transition experimental study high risk human model image guided therapy imaging agent imaging approach immunogenicity improved in vivo interdisciplinary approach men molecular imaging mortality mouse model non-invasive imaging novel outcome forecast overexpression preclinical development preclinical evaluation prevent prostate biopsy prostate cancer risk protein biomarkers safety testing social stemness success surveillance imaging tumor

项目摘要

Abstract The goal of this project is to develop a safe and effective targeted MRI contrast agent for accurate early detection and differential diagnosis of high-risk prostate cancer. Prostate cancer is a highly heterogeneous disease and the second most cause of cancer death of men in the US. Early accurate detection and differential diagnosis of high-risk prostate cancer are critical for physicians to tailor efficacious interventions to treat the disease earlier at a treatable stage. We propose to develop 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. Non-invasive high-resolution MRI of the oncoprotein holds a great promise for accurate localization and differential diagnosis of high-risk prostate cancer. The specific aims of the project are 1) to optimize peptide-targeted MRI contrast agents specific to the oncoprotein in high-risk prostate cancer and to establish mouse prostate PDX models; 2) to perform preclinical evaluation of the targeted MRI contrast agents; 3) to determine the effectiveness of the targeted MRI contrast agents for early detection and differential diagnosis of high-risk prostate cancer in animal tumor models, including patient-derived tumor models, and the toxicity of a lead targeted contrast agent. We have demonstrated the feasibility of our targeted contrast agents in detection and differential prognosis of high-risk prostate cancer in animal models. Multidisciplinary approaches will be applied by a strong research team with complementary expertise in molecular imaging, uro-oncology, pathology, cancer biology, and MRI physics from Case Western Reserve University and Cleveland Clinic in this project. We will identify a lead targeted contrast agent to initiate comprehensive preclinical and clinical development. The targeted contrast agent will have the potential to provide early detection, localization, and differential diagnosis of high-risk prostate cancer. It can also be used for risk stratification, active surveillance, and image-guide therapy of prostate cancer in clinical practice. Success in this endeavor is not limited to better clinical management of the disease, but will also provide exceptional economic and social benefit.

抽象的该项目的目的是开发安全有效的有针对性的MRI对比剂，以准确高危前列腺癌的早期检测和鉴别诊断。前列腺癌是一种高度异质性疾病和美国男性癌症死亡的第二大原因。早期准确高危前列腺癌的检测和鉴别诊断对于医生量身定制至关重要有效的干预措施可以在可治疗阶段治疗该疾病。我们建议开发小说分子成像方法靶向与上皮到间质相关的癌蛋白过渡（EMT），癌细胞干，血管生成，增殖和转移。癌蛋白具有高风险前列腺癌的肿瘤细胞外基质中的高表达，低级肿瘤中的低表达，在正常组织中没有。癌蛋白的非侵入性高分辨率MRI对高危前列腺癌的准确定位和鉴别诊断。特定目标项目是1）优化针对高风险中癌蛋白特异性肽的MRI对比剂的优化前列腺癌并建立小鼠前列腺PDX模型； 2）对临床前评估有针对性的MRI对比剂； 3）确定目标MRI对比剂的有效性在动物肿瘤模型中，早期检测和鉴别诊断，包括患者衍生的肿瘤模型以及铅靶向造影剂的毒性。我们已经证明了我们目标对比剂在检测和高危前列腺的差异预后中的可行性动物模型中的癌症。强大的研究团队将采用多学科的方法分子成像，URO肿瘤学，病理学，癌症生物学和MRI方面的互补专业知识 Case Western Reserve University和Cleveland诊所的物理学在这个项目中。我们将确定一个铅靶向对比剂，以启动全面的临床前和临床发展。目标对比剂将有可能提供早期检测，定位和鉴别诊断高危前列腺癌。它也可用于风险分层，主动监视和图像指导在临床实践中对前列腺癌的治疗。在这项工作中的成功不仅限于更好的临床该疾病的管理，但也将提供特殊的经济和社会利益。