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Response of tumors to therapy studied by 31P magnetic resonance spectroscopy
G S Karczmar1, D J Meyerhoff, A Speder
1Magnetic Resonance Unit, Veterans Administration Hospital, San Francisco, CA 94121.
Abstract:
Magnetic resonance (MR) methods have been used to study the metabolic and vascular response of model tumors to tumor necrosis factor (TNF). Magnetic resonance measurements demonstrated acute reductions in tumor blood flow, measured from tumor uptake of D2O, and in tumor adenosine triphosphate (ATP), measured by 31P magnetic resonance spectroscopy (MRS) following administration of TNF. The decrease in ATP generally followed reduction in tumor blood flow, and therefore was probably due to ischemia caused by damage to tumor vasculature. Superficial human tumors have been studied by MRS to characterize their 31P spectra, and to measure metabolic changes during therapy. The ratio of the intensities of the phosphomonoester (PME) and ATP resonances (PME/ATP) was much higher in tumors than in the normal tissue displaced by the tumors. During therapy, decreases in PME/ATP were detected that paralleled, but did not anticipate, decreases in tumor size. In some cases, a transient increase in PME/ATP was detected during therapy, which did not correlate with changes in tumor size, and which may reflect stimulation of cell growth in some tumor zones.
Insights
Magnetic resonance (MR) methods revealed that tumor necrosis factor (TNF) acutely reduces tumor blood flow and adenosine triphosphate (ATP) levels, likely causing ischemia. Changes in phosphomonoester/ATP ratios during therapy may indicate metabolic shifts and cell growth.
Area of Science:
- Biophysics
- Oncology
- Biochemistry
Background:
- Magnetic resonance (MR) methods are valuable for investigating tumor physiology.
- Tumor necrosis factor (TNF) influences tumor metabolism and vascularity.
- Phosphorus-31 magnetic resonance spectroscopy (31P MRS) can assess cellular energy status.
Purpose of the Study:
- To evaluate the metabolic and vascular responses of tumors to TNF using MR techniques.
- To characterize 31P MRS spectral changes in human tumors during therapy.
- To correlate metabolic changes with tumor response and growth.
Main Methods:
- Utilized MR imaging and 31P MRS to measure tumor blood flow (D2O uptake) and adenosine triphosphate (ATP) levels in model tumors treated with TNF.
- Studied superficial human tumors using 31P MRS to analyze 31P spectra and metabolic changes during therapy.
- Quantified the ratio of phosphomonoester (PME) to ATP (PME/ATP) in tumors and surrounding normal tissue.
Main Results:
- TNF administration led to acute reductions in tumor blood flow and ATP levels, suggesting TNF-induced vascular damage and ischemia.
- The PME/ATP ratio was significantly higher in tumors compared to normal tissue.
- During therapy, decreases in PME/ATP generally paralleled tumor size reduction, while transient increases may indicate stimulated cell growth.
Conclusions:
- MR methods, particularly 31P MRS, can monitor tumor metabolic and vascular changes in response to TNF and during therapy.
- The PME/ATP ratio serves as a potential biomarker for tumor metabolic status and response to treatment.
- Further investigation is needed to understand the implications of transient PME/ATP increases during therapy.