A major research is the identification of characteristics of individual tumors which predict their to treatment. Virtually every epithelial or mesenchymal solid rodent tumor tested has hypoxic cells. These cells are a major determinant of the tumor control probability (TCP) after radiation and some chemotherapeutic agents. The association of hypoxia and TCP has also been shown for the limited number of human tumor xenographs tested, and a variety of invasive physiological studies have demonstrated the presence of hypoxic cells in human tumors. We intend to examine tumor biochemical/physiologic state, and determine to what extent that state predicts the response to tumor to radiation. We and others have preliminary data suggesting that 31P MRS (magnetic resonance spectroscopy) can be used to measure metabolic parameters related to tumor hypoxic cell fraction (HCF) and we have recent data which demonstrates a correlation between the T (longitudinal relaxation time) of inorganic phosphate (Pi) and the percent S-phase cells. Non-invasive measurement of several tissue oxygenation related metabolic parameters including: phosphocreatine (PCr); Pi; phosphomonoesters; phosphodiesters; pH; nulceotide triphosphates; and lactate will be performed. Metabolic rate related parameters including: delta G (ATP) (free energy of hydrolysis); Mg++; free nucleotide diphosphates ((NDP)); T, of Pi and PCr; and ATPase and CK (creatine kinase) reaction rates will all be measured concurrently. An examination for correlation between these MRS parameters, and the radiation response of the same tumor is proposed. Initial studies will use C3H murine fibrosarcomas (FSaII), and mammary carcinomas (MCaIV). Single radiation fraction and two fraction experiments are planned. Radiation treatment response endpoints will include: growth delay; local and distant control for 120 days; and crude survival. These studies will be repeated using human tumors grown in nude mice. Cell replication and processes associated with replication are a primary consumer of tumor cell energy. An examination for correlation between metabolic rate related MRS parameters and percent S-phase cells is therefore planned. In these experiments the percent S-phase cells measured by flow cytometry, will be compared to metabolic rate related MRS parameters measured on the same tumor.
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