The measurement of extracellular water volumes in tissues by gadolinium modification of 1H-NMR spin lattice (T1) relaxation

The present studies were conducted in RIF-1, M5076 and Panc02 murine tumor models to compare extracellular water measurements made by 51Cr-EDTA dilution techniques and a new method which exploits the concentration dependent modification of 1H-NMR proton relaxation by Gadolinium-DTPA-dimethyl glucamine (Gd-DTPA-dimeg) in plasma and tissues. The time dependent changes in T1 modification in tissue and plasma were determined at various intervals after i.v. injection of 0.1 ml of 100 mM Gd-DTPA-dimeg and Gd concentrations determined from standard curves of Gd concentration dependent T1 modification of mouse plasma. Comparison of tissue and plasma Gd concentrations permitted the calculation of Gd-DTPA-dimeg distribution volumes. In unperturbed RIF-1, M5076 and Panc02 tumors, Gd-DTPA-dimeg distribution volumes determined by the T1 modification technique were similar to extracellular water spaces determined by 51Cr-EDTA dilution assays. In mouse liver, the 51Cr-EDTA assay resulted in artifactually high extracellular water space estimates due to internalization of the probe; Gd-DTPA-dimeg distribution volumes determined in liver with both the 153Gd-DTPA-dimeg and by the T1 modification method were approximately 150 ul/gram. The Gd-DTPA-dimeg T1 modification method also provided good approximations of changes in extracellular water volumes in RIF-1 tumors after dexamethasone and cyclophosphamide treatments. These results indicate that Gd-DTPA-dimeg modification of proton relaxation may be extremely useful for monitoring changes in tumor water dynamics during cancer therapy.