Core 5

Core 5
Therapeutic Targeting
(Director: Paul Grayburn, M.D.)

Dr. Grayburn and Shohet will make microbubbles containing adenoviral-based anti-neoplastic genes and deliver them using the ultrasound-mediated microbubble technique. This technique is novel and unique to UT Southwestern and Dr. Grayburn's laboratory. It offers the ability to test a wide variety of anti-neoplastic transgenes in a wide variety of specific tumor models. The Pre-ICMIC will provide a platform to expand future cancer research initiatives in this novel method of site-specific targeting of anti-neoplastic agents, e.g., we envision labeling the surface of the microbubbles with ligands that bind to specific tumor markers in order to further enhance the efficiency of tumor targeting with this approach. Addition of radiolabels (e.g., ¹²⁵I, ^99mTc) or MR reporters (¹⁹F, Gd-DTPA) will aid in assessing delivery. Subsequently, the activity of delivered materials will also be assessed using appropriate reporters (e.g., radiolabeled antibodies). This grant allows for new collaboration of experts in ultrasound physics, microbubble chemistry, and oncology in order to bring their specific areas of expertise to a unique solution to targeting gene therapy to tumors.

In addition to this novel mechanical delivery and targeting technique, it is clear that other non-viral mediated methods may be developed for tumor targeting. Dr. Thorpe has developed antibody targeting approaches to deliver coagulating agents to tumors and this is the basis of Development Project 1, exploiting VCAM, E-selectin and other molecular targets. The expertise of Drs. Kodadek and Corey in developing novel agents will open further approaches as specific chromosomal aberrations are identified by Dr. Minna's research and gene screening to provide new targeting agents. Furthermore, transgene methodologies of Core 6 may provide novel approaches

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Thursday, September 20, 2001

Southwestern In Vivo Cellular and Molecular Imaging Program