The central focus of this application is the completion, validation, and implementation of a novel technique recently developed in the PI's laboratory for repeated, nondestructive measurement of regional tumor blood flow (rTBF) throughout rodent tumor models. the uptake integral approach utilized minimizes the sensitivity to differences in the arterial input function and may make it possible to determine absolute TBF without sampling the arterial input function. This approach will be validated by direct comparison of total TBF measured by NMR spectroscopic observation of whole tumor HOD uptake to TBF measured by both radiolabeled microspheres and 14C-iodoantipyrine injected at essentially the same time as the D20. After completing the development of methodology to quantitate absolute rTBF from deuterium NMR images acquired after bolus intravenous injection of D20, such measurements of rTBF will be validated by comparison to rTBF measured by 14C-iodoantipyrene injected at the same time as the D20. The conditions under which absolute TBF can be measured in rodent rumors without knowledge of the arterial input function will be assessed by evaluating the variation in the arterial input function under a variety of conditions and computer simulation of the effect of such variations on measured rTBF. The potential effect of acute changes in perfusion within tumors on the use of images acquired 8 to 15 minutes after D20 injection in order to decrease the limit of rTBF detection for the uptake method will be assessed by determining both the fraction of the tumor affected and the time scale of transient perfusion using the double fluorescent dye technique in tumors from which HOD uptake data is simultaneously acquired. The effect on rTBF of tumor size and transplantation site will be evaluated to determine if changes in the rTBF distribution with size are dependent on transplantation site. Since tumors are seldom homogeneously perfused and TBF can both affect the response of a tumor to therapy and be altered by therapy, this technique should be an extremely valuable tool to further our understanding of the relationship between TBF and therapeutic response.
