A noninvasive technique has been advanced for measurement and characterization of tissue perfusion properties in situ. The technique, called Proton-Activated Positron Emission (PAPE), has several unique capabilities: (1) Simultaneous quantification of tumor blood flow (TBF) as well as well-perfused or mobile fraction (MF) in tumors. Mobile fraction or its change following therapy may have physiologic or pathologic significance. (2) Determination of the same perfusion parameters in an entire solid tumor or in selected regions of a tumor. This feature permits study of perfusion heterogeneity within a tumor. Most of the technical aspects of PAPE have been developed in this laboratory and pilot studies using the technique for murine tumors are promising. However, the technique needs further refinement and its potential applications have not been validated. The overall goal of this proposal is two-fold. First, we plan to verify the PAPE technique by comparing the TBF so obtained to the measurements made by two other established techniques. The radioactive microsphere technique is the reference to the employed for the rat rhabdomyosarcomas in order to account for cardiac output. A second reference technique will be selected from the Xenon-133 washout or the Rb- 86 wash-in methods depending upon the outcome of our initial experiences. The second reference is used primarily for technique comparison in murine tumors (KHT and RIF-1). The second objective is to study the effects of fast neutrons on the perfusion properties in KHT and RIF-1 tumors, relative to x-irradiation, using the PAPE technique. There is a dearth of information in the literature concerning high-LET radiation effects on TBF. The long-term goal is to seek a better understanding of the relationship between radiation-induced changes in tumor perfusion characteristics and reoxygenation of tumor cells, especially pertaining to the radiobiologically hypoxic population.
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