Various inhibitors of polyamine and histamine synthesizing enzymes characteristic of tumors will be assayed for potential use in conjunction with radiolabeled polyamines in tumor imaging. Initially, polyamines and analogues labeled with C-14, H-3 or I-131 will be evaluated for tumor localization in mice depleted of polyamines by pre-administration of appropriate inhibitors. Also, a H-3 and/or C-14 labeled inhibitor will be synthesized and assayed for tumor localization. The radioactivity distribution from the amines and inhibitor will be optimized by varying diets, routes of administration and schedules of doses. Then, tumor localization will be assessed in various tumors of different tumor ages, and degrees of malignancy. The most promising materials labeled with H-3, C-14 or I-131 will be labeled with C-11, F-18 or I-131 for administration to larger animals bearing tumors for tumor imaging by external scintigraphy. In addition to providing a technique for tumor detection and for monitoring progress of tumor growth or regression, this research could provide further insight into the in vivo function and mechanism of action of polyamines. A very important fringe benefit possible from this research is that conditions would be developed which would enhance the tumor uptake of properly selected polyamine linked chemical moieties having anticancer activity. The synthetic work will apply well established chemical knowledge to the development of novel radiolabeled compounds. The project involves radiopharmacology, biochemistry and bioorganic chemistry.
| Digenis, G A; Hawi, A A; Yip, H et al. (1986) Detection of tetrafluoroputrescine in RBCs by fluorine-19 nuclear magnetic resonance spectroscopy. Life Sci 38:2307-9 |
