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. ? ? ?
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| Towner, Rheal A; Smith, Nataliya; Asano, Yasuko et al. (2010) Molecular magnetic resonance imaging approaches used to aid in the understanding of angiogenesis in vivo: implications for tissue engineering. Tissue Eng Part A 16:357-64 |
| Towner, Rheal A; Smith, Nataliya; Asano, Yasuko et al. (2010) Molecular magnetic resonance imaging approaches used to aid in the understanding of the tissue regeneration marker Met in vivo: implications for tissue engineering. Tissue Eng Part A 16:365-71 |
| Towner, R A; Smith, N; Doblas, S et al. (2008) In vivo detection of c-Met expression in a rat C6 glioma model. J Cell Mol Med 12:174-86 |
