31P Surface‐Coil NMR Analysis of Metabolic Status in KHJJ Tumors

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 monotoring 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/P_i 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 P_i. As the tumor volume increased above 1 cm³, ATP/P_i 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 P_i, was found to vary in these tumors from 7.1 in rapidly metabolizing tissue to 6.6 in necrotic tumors.© 1985 Academic Press,Inc.