Enable Early and Sensitive In Vivo Detection of Liver Metastasis by Protein-based

通过基于蛋白质的方法实现肝转移的早期、灵敏的体内检测

• 批准号: 8714923
• 负责人: Jenny J. Yang
• 金额: $ 22.5万
• 依托单位: INLIGHTA BIOSCIENCES, LLC
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8714923
• 关键词: Ablation; Address; Affinity; Albumins; Animals; Antibodies; Binding; Binding Sites; Biological Markers; CXCR4 gene; Cell Line; Cessation of life; Clinical; Contrast Media; Death Rate; Detection; Development; Diagnosis; Disease; Dose; Drug Kinetics; Drug or chemical Tissue Distribution; ERBB2 gene; Early Diagnosis; Effectiveness; Exhibits; Goals; Histology; Image; Image Guided Biopsy; Image-Guided Surgery; Ions; Lasers; Lesion; Liver; Liver neoplasms; Magnetic Resonance Imaging; Malignant Neoplasms; Malignant neoplasm of liver; Mammary Neoplasms; Marketing; Melanoma Cell; Metals; Metastatic Melanoma; Metastatic Neoplasm to the Liver; Methodology; Modeling; Monitor; Mus; Neoplasm Metastasis; Patient Selection; Patients; Penetration; Pentetic Acid; Phase; Physiological; Post-Translational Protein Processing; Primary Neoplasm; Property; Prostatic Neoplasms; Proteins; Reagent; Reporting; Research; Resistance; Resolution; Risk; Safety; Sensitivity and Specificity; Small Business Technology Transfer Research; Staging; Toxic effect; Transplantation; Tumor Burden; Tumor Tissue; Uveal Melanoma; Xenograft procedure; Yang; base; clinical application; crosslink; design; imaging modality; immunogenicity; improved; in vivo; in vivo imaging; liver transplantation; melanoma; molecular imaging; mouse model; neoplastic cell; novel; phase 2 study; preference; public health relevance; ratiometric; response; treatment strategy; tumor; tumor specificity

DESCRIPTION (provided by applicant): The major barriers limiting the application of MRI to detect small liver lesions and metastasis at the early stage and patient selection for targeted therapy based on molecular imaging of disease biomarkers, are due to the lack of desired MRI contrast agents capable of enhancing the contrast between normal liver tissues and tumors with high relaxivity, tumor targeting, high intra-tumoral distribution and no toxicity. The low sensitivty related to low relaxivity of the current clinically approved contrast agents has posted additional limitations to the further application of MRI to monitor the effect of metastasis treatment, including image-guided laser ablation. To address the critical need, We (Dr. Jenny J. Yang's team in Atlanta) have developed a novel class of protein-based MRI contrast agents which exhibit significant improvement of both r1 and r2 relaxivities compared to the clinical MRI contrast agents, an improvement in in vivo dose efficiency in mouse models, is capable of in vivo imaging with T2/T1 ratiometric changes, and low toxicity and immunogenicity. The goal of STTR Phase I research is to obtain proof-of- principle evidence to achieve early detection of liver tumor and metastasis of uveal melanoma with significantly improved sensitivity and selectivity by optimizing and characterizing our designed protein-based contrast agents (ProCAs) with liver preference and tumor specificity. Aim 1 is to develop liver-specific tumor imaging contrast agents with desired stability and sensitivity using a transplanted mouse model. Aim 2 is to develop liver tumor-specific molecular imaging contrast agent with high accuracy using transplanted and orthotropic melanoma metastasis models. Comparisons with clinically approved MRI contrast agent Eovist/Primost and detailed histology analysis will be performed. In Phase II studies, we will investigate safety, immunogenicity, and their effectiveness in monitoring responses to targeted therapies and application to image-guided surgery. These proposed studies will provide necessary results for transition to clinical application for liver metastasis.

描述（由申请人提供）：主要障碍限制了MRI在早期阶段检测小肝病病变和转移，以及基于疾病生物标志物的分子成像的靶向治疗的患者选择，这是由于缺乏所需的MRI对比剂，无法增强正常肝组织和较高的肿瘤对较高的较高的肿瘤，较高的肿瘤，较高的肿瘤，较高。与当前临床批准的对比剂的低松弛度有关的低敏感性对进一步应用MRI的进一步限制在监测转移治疗的效果（包括图像引导的激光消融）方面存在额外的限制。 To address the critical need, We (Dr. Jenny J. Yang's team in Atlanta) have developed a novel class of protein-based MRI contrast agents which exhibit significant improvement of both r1 and r2 relaxivities compared to the clinical MRI contrast agents, an improvement in in vivo dose efficiency in mouse models, is capable of in vivo imaging with T2/T1 ratiometric changes, and low toxicity and immunogenicity. STTR I期研究的目的是获得原理证据证据，以通过优化和表征具有肝偏好和肿瘤特异性的我们设计的基于蛋白质的对比剂（PROCAS），以优化和表征我们设计的基于蛋白质的对比剂（PROCAS），以显着提高尿肿瘤和紫veal黑色素瘤的转移，从而显着提高敏感性和选择性。目的1是使用移植小鼠模型开发具有所需稳定性和灵敏度的肝脏特异性肿瘤成像对比剂。 AIM 2是使用移植和正性性黑色素瘤转移模型以高精度开发肝肿瘤特异性分子成像对比剂。将进行与临床批准的MRI对比剂EOVIST/PRIMOST和详细的组织学分析的比较。在第二阶段的研究中，我们将研究安全性，免疫原性及其在监测对靶向疗法的反应和对图像引导手术的应用中的有效性。这些提出的研究将为过渡到肝转移的临床应用提供必要的结果。