The major objective of this project is to identify biological processes and radiochemical tracers ulitmately useful in nuclear imaging of tumors and to use this information in tumor diagnosis as well as the monitoring of response to fractionated radiation therapy. Biological processes which are quantitatively different, but not qualitatively unique, in tumors will be investigated, using mouse tumor and cell culture systems.
The specific aims are as follows. (1) The biological basis for uptake of the tumor imaging radionuclide gallium-67 in control and irradiated tumor cells in vitro and tumors in vivo via a transferrin (Tf) receptor will be studied, testing the hypotheses that growth state is the principal determinent of Tf receptor number; postradiation growth changes may alter number of cell surface Tf receptors; and Tf-mediated uptake of iron is a major competitor in gallium-67 uptake. (2) The metabolically induced binding of labelled hypoxic cell radiation sensitizing drugs in hypoxic cells will be studied as a basis for imaging radiation resistent, oxygen-deprived tumor regions. (3) Uptake of labelled DNA and glycolysis precurosors will be investigated as an indicator of the feasibility of positron imaging of tumors. These biological phenomena are chosen for two reasons. First, tumors are likely to differ quantitatively from many normal tissues in having increased cell proliferation (higher DNA synthesis rates, more cell surface Tf receptors), increased glycolysis, and a proportion of hypoxic cells. Second, the concept of """"""""metabolic trapping"""""""" applies to certain precursors of DNA synthesis and glycolysis and probably to the hypoxic cell sensitizers as well. Repopulation of tumor cells between doses of radiation and reoxygenation of formerly hypoxic cells are two major modifiers of tumor response to fractionated radiotherapy and these phenomena are amenable to study by the approaches outlined above.
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