Tumor imaging will be advanced by studying the uptake of particles in malignant tumors. The pharmacodynamics of concentrated emulsions of perfluorooctylbromide (PFOB) will be determined by measuring the distribution, metabolism and elimination patterns of PFOB in tumors, liver and spleen in mice, rats and rabbits. This information will be used to determine the optimal timing and dose for imaging. Concentrations of PFOB will be measured by gas chromatography and X-ray fluorescent spectroscopy. Distribution patterns will be assessed by low voltage X-ray. CT scans or MRI. Microscopic examination will be used to determine localization of emulsion particles. Methods to facilitate the uptake of PFOB in the tumor macrophages will be explored by breathing the tumored mice on increased concentrations of O2 following administration of PFOB emulsion which is also an excellent oxygen delivery system. Other response modifying agents will also be used such as cosurfactants, fluorosurfactants, hormones, monokines and other compounds in order to increase tumor concentrations of PFOB. The tolerance of these modified emulsions will be measured by standard toxicological techniques. Additional investigations will be performed to study the mechanisms by which the tumor macrophage population and function is altered by the administration of fluorochemical emulsions. The number of phagocyte cells in the proliferation phase will be estimated by labeling cells with tritiated thymidine. The source of the rapidly proliferating cells will be studied by radiation therapy with selective shielding of the tumor during whole body radiation and shielding of the body during tumor radiation.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA032857-12
Application #
3170725
Study Section
Diagnostic Radiology Study Section (RNM)
Project Start
1979-01-01
Project End
1992-03-31
Budget Start
1991-04-05
Budget End
1992-03-31
Support Year
12
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Type
Schools of Medicine
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Long Jr, D M; Vasquez, F; Witt, B L et al. (1992) Cyclooxygenase inhibition with ibuprofen: effect on biodistribution of perflubron emulsions in mice with mammary tumor. Biomater Artif Cells Immobilization Biotechnol 20:911-4
Long, D M; Witt, B L; Escobar, J A et al. (1992) Effect of emulsion concentration on biodistribution of perflubron in tumor-bearing mice. Biomater Artif Cells Immobilization Biotechnol 20:907-10