The main objective of this application is to critically evaluate the potential for in vivo 31P and 1H NMR spectroscopy to provide a noninvasive, predictive assay of tumor response to radiation therapy before and/or during the course of treatment. Because NMR is nondestructive, the methodology developed and evaluated in these studies, using a murine tumor system, can be applied in the clinic. A clinical predictor of radiation response should: i) aid in the selection of groups for clinical trials of new treatment protocols targeted for radioresistant tumors thereby maximizing the probability of identifying effective treatment strategies; and ii) allow the response in individual patients to be utilized in designing more effective, individualized therapy. A special emphasis is placed on examining the relationship between radiobiological hypoxia and the NMR metabolic characteristics. The in vivo relationship will be examined by a direct comparison of the NMR metabolic characteristics and the radiobiological hypoxic fraction determined in the same tumor-bearing mice. The presence and importance of contributions to the NMR signal from cells which are not radiobiologically hypoxic, but have similar NMR metabolic characteristics, will be evaluated by: i) examining the relationship between the NMR metabolic characteristics and cellular radiosensitivity as a function of both PO2 and the length of time spent under hypoxic conditions in a system which allows NMR observation of tumor cells in a controlled, homogeneous environment (i.e., in vitro); and ii) examining the effects of the fraction of necrotic cells on the relationship between the NMR metabolic characteristics and the radiobiological hypoxic fraction in a system which allows NMR observation of tumor cells in a heterogeneous environment mimicing that found in tumors, but with control over the degre of heterogeneity (i.e., in spheroids). The hypoxic fraction information obtained from both NMR and measurement of radiolabeled-misonidazole binding will be compared by applying both techniques to the same tumor-bearing mice. The predictive ability of NMR will be evaluated by comparing the radiation response of individual tumor-bearing mice with their NMR metabolic characteristics and the changes in those characteristics in reponse to treatment, but before marked decreases in tumor size.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
3R01CA043113-01S1
Application #
3185034
Study Section
Diagnostic Radiology Study Section (RNM)
Project Start
1986-08-01
Project End
1990-01-31
Budget Start
1986-08-01
Budget End
1988-01-31
Support Year
1
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Wayne State University
Department
Type
Schools of Medicine
DUNS #
City
Detroit
State
MI
Country
United States
Zip Code
48202
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Simpson, N E; Evelhoch, J L (1999) Deuterium NMR tissue perfusion measurements using the tracer uptake approach: II. Comparison with microspheres in tumors. Magn Reson Med 42:240-7
Simpson, N E; He, Z; Evelhoch, J L (1999) Deuterium NMR tissue perfusion measurements using the tracer uptake approach: I. Optimization of methods. Magn Reson Med 42:42-52
Zhao, M; Pipe, J G; Bonnett, J et al. (1996) Early detection of treatment response by diffusion-weighted 1H-NMR spectroscopy in a murine tumour in vivo. Br J Cancer 73:61-4
Zhao, M; Fortan, L G; Evelhoch, J L (1995) The effects of isoflurane and halothane on blood flow and 31P NMR spectra in murine RIF-1 tumors. Magn Reson Med 33:610-8
Evelhoch, J L (1992) Measurement of tumor blood flow by deuterium NMR and the effects of modifiers. NMR Biomed 5:290-5
Evelhoch, J L; McDouall, J B; Mattiello, J et al. (1992) Measurement of relative regional tumor blood flow in mice by deuterium NMR imaging. Magn Reson Med 24:42-52
Mattiello, J; Evelhoch, J L (1991) Relative volume-average murine tumor blood flow measurement via deuterium nuclear magnetic resonance spectroscopy. Magn Reson Med 18:320-34
Larcombe McDouall, J B; Evelhoch, J L (1990) Deuterium nuclear magnetic resonance imaging of tracer distribution in D2O clearance measurements of tumor blood flow in mice. Cancer Res 50:363-9
Evelhoch, J L; McCoy, C L; Giri, B P (1989) A method for direct in vivo measurement of drug concentrations from a single 2H NMR spectrum. Magn Reson Med 9:402-10