The potential utility of chemical radioprotection of normal tissues in radiation therapy is critically dependent on both maximizing radioprotection of normal tissues and minimizing protection of tumors. Our overall objective is to investigate the mechanisms of differential radioprotection with the goal of better defining the conditions and treatment parameters for maximum radioprotection of normal tissues and minimal radioprotection of tumors. These studies will be carried out as a comparison of the standard radioprotector, WR-2721, with WR-3689, which appears in preliminary studies to be at least as effective.
Our specific aims are to determine: 1). Does tumor protection increase as radiation fraction size decreases? 2). Does WR-2721 or WR-3689 increase hypoxia in tumors or normal tissues? 3). Does WR-2721 or WR-3689 alter the time-course of tumor reoxygenation between radiation fractions? 4). Are the dephosphorylated products of WR-2721 and WR-3689 effective tumor protectors? 5). How effective is WR-3689 in comparison with WR-2721 in protecting the kidney?
| Coia, L R; Brown, D Q; Hardiman, J (1988) WR-2721 as cytotoxic and radioprotective agent in treatment of murine lymphoma with total body irradiation. NCI Monogr :235-9 |
| Brown, D Q; Graham 3rd, W J; MacKenzie, L J et al. (1988) Can WR-2721 be improved upon? Pharmacol Ther 39:157-68 |
| Brown, D Q; Shaw, L M; Pittock 3rd, J W et al. (1986) Modification of WR-2721 toxicity and radioprotection by an inhibitor of alkaline phosphatase. Int J Radiat Oncol Biol Phys 12:1491-3 |
