We propose to study five interrelated themes in order to develop basic knowledge on relaxation in tissues with the aim of applying these findings to improve clinical and research use of in vivo NMR. The themes of our research are: 1) proton relaxation in lipids, 2) the effect of oxygen on proton relaxation, 3) use of nitroxide free radicals to modify proton relaxation rates 4) the detection and use of altered redo states in tissues to enhance contrast, 5) the use of liposomes to model tissue processes and deliver contrast agents. Our primary experimental approach is to measure proton relaxation by obtaining a full NMR dispersion profile of T1 values from .01MHz to 50MHz. The measurement and modification of relaxation in lipids should provide the basis to use relaxation data from lipid protons to follow physiological and pathological changes. The use of oxygen as a contrast agent will be studied with an emphasis on effects in lipids because of the 4-fold increased solubility of oxygen in lipids. The chemical versatility of nitroxides provides potential advantages as contrast agents, including the use of lipid seeking nitroxides and optimization of solubility and/or water binding properties of nitroxides to increase relaxation. Areas of altered redox states may be detected by virtue of their different oxygen tension and/or effects on the activity of nitroxides. Liposomes provide potential means to deliver contrast agents with reduced toxicity and increased specificity. The team that will carry out these studies have extensive experience in the technology needed to carry out this proposal, including magnetic resonance relaxation, electron spin resonance and nitroxides and liposomes. Preliminary experiments have demonstrated the feasibility of these studies.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA040665-02
Application #
3180967
Study Section
(SSS)
Project Start
1985-09-30
Project End
1988-07-31
Budget Start
1986-09-30
Budget End
1987-07-31
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Illinois Urbana-Champaign
Department
Type
Schools of Medicine
DUNS #
041544081
City
Champaign
State
IL
Country
United States
Zip Code
61820
Bacic, G; Niesman, M R; Magin, R L et al. (1990) NMR and ESR study of liposome delivery of Mn2+ to murine liver. Magn Reson Med 13:44-61
Bennett, H F; Brown 3rd, R D; Keana, J F et al. (1990) Interactions of nitroxides with plasma and blood: effect on 1/T1 of water protons. Magn Reson Med 14:40-55
Chan, H C; Sun, K Q; Magin, R L et al. (1990) Potential of albumin labeled with nitroxides as a contrast agent for magnetic resonance imaging and spectroscopy. Bioconjug Chem 1:32-6
Bacic, G; Alameda Jr, J C; Iannone, A et al. (1989) NMR study of water exchange across the hepatocyte membrane. Magn Reson Imaging 7:411-6
Enochs, W S; Hyslop, W B; Bennett, H F et al. (1989) Sources of the increased longitudinal relaxation rates observed in melanotic melanoma. An in vitro study of synthetic melanins. Invest Radiol 24:794-804
Chan, H C; Magin, R L; Swartz, H M (1989) Rapid assessment of liposomal stability in blood by an aqueous nitroxide spin label. J Biochem Biophys Methods 18:271-6
Federico, M; Iannone, A; Chan, H C et al. (1989) Bone marrow uptake of liposome-entrapped spin label after liver blockade with empty liposomes. Magn Reson Med 10:418-25
Chan, H C; Magin, R L; Swartz, H M (1988) Delivery of nitroxide spin label to cultured cells by liposomes. Magn Reson Med 8:160-70
Bacic, G; Niesman, M R; Bennett, H F et al. (1988) Modulation of water proton relaxation rates by liposomes containing paramagnetic materials. Magn Reson Med 6:445-58
Bennett, H F; Swartz, H M; Brown 3rd, R D et al. (1987) Modification of relaxation of lipid protons by molecular oxygen and nitroxides. Invest Radiol 22:502-7

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