Abstract
Noninvasive monitoring of the effects of treatment on cancer tissue is fundamental to the development of rational radioimmunotherapy (RIT) schemes employing radiolabeled monoclonal antibodies or antibody fragments specific for human cancer. Recent advances in nuclear magnetic resonance spectroscopy make it an attractive candidate for sequential, topical monitoring by 31P NMR of metabolic events during RIT. Preliminary to this effort, we examined the metabolic competence of the well-characterized, murine KHJJ tumor in situ in BALB/c mice using 31P surface-coil NMR. The ATP/Pi ratio in tumor volumes ranging from 100 to 800 mm3 showed that tumors over this range of sizes were able to maintain high levels of ATP relative to Pi. As the tumor volume increased above 1 cm3, ATP/Pi levels indicated poor metabolic competence. This lack of metabolic competence was correlated with histological evidence of tissue necrosis and vascular disintegration. The T1 values of assigned phosphorus metabolites were established. Intracellular pH, as determined from the chemical shift of Pi, was found to vary in these tumors from 7.1 in rapidly metabolizing tissue to 6.6 in necrotic tumors.
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