Full Project 1: Tumor-targeted MR Contrast Enhancement Using Molecular Imaging Te

Johns Hopkins University, Baltimore MD

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Abstract

Magnetic resonance molecular imaging strategies have been explored by specifically targeting[unreadable] oncogenes such as HER-2 (c-erbB-2, Neu), bcl-2/bcl-xL, protein kinase A, and the transferrin receptor[unreadable] gene. The human transferrin receptor (hTfR) has been used as a molecular target to direct therapeutic[unreadable] agents to tumor cells and to shuttle drugs across the blood-brain barrier. Expression and regulation of[unreadable] hTfR'receptors can be visualized by NMR imaging by studying the receptors with a sterically protecting[unreadable] iron-containing magnetic hTfR probe. A cationic immunoliposome system which covalently conjugates[unreadable] the single-chain antibody variable region fragment (scFv) against the hTfR has been used to improve[unreadable] p53 tumor suppressor gene therapy employed in the human breast cancer metastasis model. This[unreadable] scFv-immunolipdsome can systematically deliver the complexed gene to tumors in vivo. In comparison[unreadable] to a whole antibody or transferrin molecule, scFv has a much smaller size, enabling it to penetrate more[unreadable] easily through solid tumors. In this study, we will utilize the TfR scFv-immunoliposome along with MR[unreadable] contrast agents to improve contrast agent-tumor affinity and specificity. This will enhance MR[unreadable] diagnostic imaging capabilities, particularly those needed for early detection.