The long rang goal of this project is to use animal model systems to evaluate the potential value of perfluorochemical emulsions (PFC-E) as adjuncts to radiotherapy and to provide the background information needed to design and implement clinical rials testing these agents. The studies proposed in this five year renewal application will focus on studies of second generation PFC-E, having characteristics more appropriate for use as adjuncts to cancer therapy than the lead compound (Fluosol) used in our initial laboratory studies and in all past and ongoing clinical trials. Studies with transplanted tumors in rats and mice will be extended to assess fractionated treatment regimens which more closely model those used in clinical radiotherapy and to determine the optimal parameters for administering PFC-E during such regimens. The potential value of multi-agent regimens combining PFC-E with hypoxic cell sensitizers or drugs toxic to hypoxic cells will be examined, to assess whether the use of multiple agents directed against hypoxic cells, which may target different hypoxic cell populations, offer the potential for greater therapeutic benefit. The biological bases of observed changes in tumor response will be examined, to assess whether factors other than changes O2 delivery to tumor cells are important to the effects of the PFC-E. Effects of second generation perfluorochemical emulsions on the radiation responses of normal tissues (bone marrow, skin, lung and bone) will be examined so that the potential for obtaining therapeutic gain with these agents can be assessed. The effects of these PFC-E on tumor growth and progression will also be examined, to ensure that these agents have no unexpected effects on the malignancies. Data from these studies will be used to help design clinical trials testing second generation PFC-E as adjuncts to radiotherapy.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA035215-11
Application #
2088884
Study Section
Experimental Therapeutics Subcommittee 1 (ET)
Project Start
1984-05-01
Project End
1996-05-31
Budget Start
1994-06-01
Budget End
1996-05-31
Support Year
11
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Yale University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
Rockwell, S (1994) Perfluorochemical emulsions and radiation therapy. Artif Cells Blood Substit Immobil Biotechnol 22:1097-108
Rockwell, S; Kelley, M; Irvin, C G (1992) Effects of the perfluorochemical emulsion FMIQ on the radiation response of EMT6 tumours. Int J Radiat Biol 61:833-9
Rockwell, S; Irvin, C G; Kelley, M et al. (1992) Effects of hyperbaric oxygen and a perfluorooctylbromide emulsion on the radiation responses of tumors and normal tissues in rodents. Int J Radiat Oncol Biol Phys 22:87-93
Sostman, H D; Rockwell, S; Sylvia, A L et al. (1991) Evaluation of BA1112 rhabdomyosarcoma oxygenation with microelectrodes, optical spectrophotometry, radiosensitivity, and magnetic resonance spectroscopy. Magn Reson Med 20:253-67
Rockwell, S; Kelley, M; Irvin, C G et al. (1991) Modulation of tumor oxygenation and radiosensitivity by a perfluorooctylbromide emulsion. Radiother Oncol 22:92-8
Rockwell, S; Hughes, C S; Kennedy, K A (1991) Effect of host age on microenvironmental heterogeneity and efficacy of combined modality therapy in solid tumors. Int J Radiat Oncol Biol Phys 20:259-63
Morton, J D; Porter, E; Yabuki, H et al. (1990) Effects of a perfluorochemical emulsion on the response of BA1112 rat rhabdomyosarcomas to continuous low-dose-rate irradiation. Radiat Res 124:178-82
Rockwell, S; Moulder, J E (1990) Hypoxic fractions of human tumors xenografted into mice: a review. Int J Radiat Oncol Biol Phys 19:197-202
Suit, H D; Rockwell, S; Zeitman, A et al. (1989) Quantitative transplantation assays of the rat rhabdomyosarcoma BA1112 isografts into the WAG/Rij Y rat and xenotransplantation into the athymic NCr (nu/nu) nude mouse. Eur J Cancer Clin Oncol 25:1463-6
Rockwell, S; Kelley, M (1989) Radiation enhancement of lung nodule formation in mice is not potentiated by treatment with a perfluorochemical emulsion and carbogen. Radiother Oncol 14:49-53

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