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：
9327104
负责人：
ZHENG-RONG LU
金额：
$ 42.34万
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/9327104
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 Imagery 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 Oncoproteins Pathology Patient Care Patients Peptides Physicians Physics Physiological Positron-Emission Tomography Prostate Prostate Cancer therapy Prostate-Specific Antigen Prostatic Neoplasms Research Resolution Risk Risk stratification Safety Signal Transduction Specimen Testing Time Tissues Toxic effect Tumor Tissue Tumor-Derived Ultrasonography Universities 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 image guided therapy imaging agent imaging approach immunogenicity improved in vivo interdisciplinary approach men molecular imaging mortality mouse model non-invasive imaging novel oncology outcome forecast overexpression preclinical development preclinical evaluation prevent prostate biopsy protein biomarkers safety testing screening social stemness success tool 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.

抽象的该项目的目标是开发一种安全有效的靶向 MRI 造影剂，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，是美国男性癌症死亡的第二大原因。早准高危前列腺癌的检测和鉴别诊断对于医生制定针对性治疗方案至关重要在可治疗阶段尽早采取有效的干预措施来治疗疾病。我们建议开发一部小说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。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，正常组织中没有。癌蛋白的非侵入性高分辨率 MRI 具有广阔的前景高危前列腺癌的准确定位和鉴别诊断。该计划的具体目标项目是 1) 优化针对高风险癌蛋白的肽靶向 MRI 造影剂前列腺癌并建立小鼠前列腺PDX模型； 2) 进行临床前评估靶向 MRI 造影剂； 3) 确定靶向 MRI 造影剂的有效性动物肿瘤模型中高危前列腺癌的早期检测和鉴别诊断，包括患者来源的肿瘤模型，以及先导靶向造影剂的毒性。我们已经证明了我们的靶向造影剂在高危前列腺检测和鉴别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方法分子成像、泌尿肿瘤学、病理学、癌症生物学和 MRI 方面的互补专业知识凯斯西储大学和克利夫兰诊所的物理学教授参与了该项目。我们将确定一个领导靶向造影剂启动全面的临床前和临床开发。所针对的造影剂将有可能提供早期检测、定位和鉴别诊断高危前列腺癌。它还可用于风险分层、主动监测和图像引导前列腺癌的临床治疗。这项努力的成功不仅限于更好的临床控制疾病的同时，还将带来非凡的经济和社会效益。