Molecular-Specific Detection of Tumors: MRI Investigations

描述(申请人提供)：该项目专注于开发和评估新型的肿瘤抗原特异性磁共振成像(MRI)分子探针，用于体内检测肿瘤抗原，这些分子探针可能作为早期发现人类恶性肿瘤的诊断生物标志物。转基因小鼠肝癌模型将被用来跟踪肿瘤结节、腺瘤和肿瘤发展过程中的连续变化。这项研究将有助于开发体内检测恶性肿瘤形成的诊断方法。具体地说，我们计划测试肿瘤特异性抗原MRI分子靶向剂的体内特异性，以便能够在小鼠肝肿瘤模型中通过靶向与肿瘤恶性相关的抗原来检测和逐步跟踪肿瘤的形成。目的：用肿瘤特异性抗体免疫组织化学方法检测肿瘤特异性抗原在小鼠肝癌细胞系(BW1J、HEPA 1-6或MH-224)中的表达程度。目的：研制肿瘤抗原特异性磁共振造影剂(含Gd或氧化铁母体化合物)，标记肿瘤特异性肿瘤标志物抗体。目的：利用磁共振成像初步确定抗原特异性造影剂对不同小鼠肝癌细胞系体外抗原结合的特异性。特异性目的2：利用抗原特异性磁共振造影剂检测实验性小鼠致癌模型体内肿瘤抗原：目的4：利用抗原特异性磁共振造影剂检测和预测实验性啮齿动物致癌模型体内肿瘤的形成。目的：比较体内MRI检测小鼠肝切片肿瘤特异性分子标志物与常规免疫组织化学检测肿瘤特异性抗原和肿瘤分级的差异。一旦我们在小鼠肝癌发生模型中建立了最佳的分子靶向制剂，那么就为启动人类细胞和规划肝癌患者的临床评估奠定了基础。

DESCRIPTION (provided by applicant): This project is focussed on developing and assessing novel tumor antigen-specific magnetic resonance imaging (MRI) molecular probes for the in vivo detection of tumor antigens, which may serve as diagnostic biomarkers for early detection of malignant human cancers. A transgenic mouse hepatocarcinogenesis model will be used to follow sequential changes during neoplastic nodule, adenoma and carcinoma development. This research will aid in the development of diagnostic methods for in vivo detection of malignant tumor formation. Specifically, we plan to test the in vivo specificity of tumor-specific antigen MRI molecular targeting agents to be able to detect and progressively follow the formation of tumors by targeting antigens associated with tumor malignancy during various stages of experimental carcinogenesis in a mouse liver tumor model. SPECIFIC AIM 1: To determine the specificity of novel MRI molecular targets for tumor antigens in mouse hepatoma cell culture models: Objective 1: Determine the degree of expression of malignant-specific tumor antigens in mouse hepatoma cell lines (BW1J, HEPA 1-6 or MH-224) using immunohistochemistry with antibodies specific for the malignant-specific tumor antigens. Objective 2: Develop tumor antigen specific MRI contrast agents (with gadolinium (Gd) or iron oxide parent compounds) tagged with an anti-nodule/tumor marker antibody (Ab) specific for malignant-specific tumor antigens. Objective 3: To use MRI to initially determine the effectiveness of the antigen-specific contrast agents for antigen-binding specificity in various mouse hepatocellular carcinoma cell lines in vitro. SPECIFIC AIM 2: Use antigen specific MRI contrast agents to detect tumor antigens in vivo within experimental mouse carcinogenesis models: Objective 4: Use antigen specific MRI contrast agents to detect and predict the formation of tumors in vivo in experimental rodent carcinogenesis models. Objective 5: To compare in vivo MRI detection of tumor-specific molecular markers with conventional immunohistoehemistry of mouse liver slices for malignant-specific tumor antigens, and tumor grading. Once we have established the optimal molecular-targeting agent in a mouse hepatocarcinogenesis model, then the groundwork is established for initiation of human cell and planning of clinical evaluations for patients with liver cancer.