Quantification of Glucose Utilization in an Experimental Brain Tumor Model by the Deoxyglucose Method

Abstract

Summary: Reevaluation of lumped and rate constants is necessary when Sokoloff's 2-deoxyglucose (DO) method is used to measure glucose utilization in pathological tissue. We describe here a modification of Sokoloff's lumped constant measurement that permits simultaneous estimation of both lumped and rate constants from a single animal experiment. A subcutaneous tumor model (AA ascites tumor) was used for measurement of these constants with a procedure similar to Sokoloff's that kept the plasma tracer concentration constant. Measured con stants were as follows: lumped constant, 0.654 ± 0.081; kj, 0.196 ± 0.038 min-I; k'!J, 0.262 ± 0.067 min-I; kj, 0.117 ± 0.044 min -I. These constants were used to quan tify glucose utilization in the implanted brain tumor. To test the validity of this method, we compared a fractionThe 2-deoxyglucose (DG) method originally de veloped by Sokoloff et al. (1977) for measurement of the local cerebral metabolic rate for glucose is widely applied in animal studies employing the au toradiographic technique and in human studies em ploying positron emission tomography (P ET).When applied to pathological tissue, this method requires reevaluation of the lumped and rate con stants that appear in the operational equation (Eq. 1, below) for quantitative measurement of the glu cose utilization rate (Sokoloff, 1979). However, their measurement is only occasionally performed, as it requires a number of matched animals and the application of a complex mathematical operational equation on the time course of tissue and blood

Deoxyglucose Kinetics in a Rat Brain Tumor

“…5. with the operational equations using the K ' s deter mined from the kinetic data vs. using the literature values of the K ' s for grey matter. This is consistent with a similar demonstration by Kato et al (1985).…”

“…The LC in malignant brain tumor tissue may not be equal to the value in normal brain tissue. Kato et al (1985) found the LC of an AA ascites flank tumor to be 0.654. Others have presented data and arguments that show that the LC is increased under conditions of hypoglycemia or ischemia, i.e., when glucose utilization is influenced more by transport limitation than by hexokinase activity (Sokoloff et aI., 1977;Crane et aI., 1983;Pardridge et aI., 1982).…”

“…Because of the present results, admittedly in an experimental brain tumor model, we raise some concern that applying normal tissue values for LC and K's to calculate glucose metabolic rate in gliomas may lead to a distinct overestimation of the true tumor glucose metabolic rate. Kato et al (1985) have also expressed this concern and have sug gested that it may be possible to evaluate rate con stants and the lumped constants in human tumors by implantation in athymic mice.…”

Relationship between of blood flow, glucose metabolism, protein synthesis, glucose and ATP content in experimentally-induced glioma (RG12.2) of rat brain

“…In small tumors, TBF did not differ from that of surrounding brain tissue whereas in large tumors it was significantly lower, especially in the center of the tumor mass [34,36,40,[42][43][44]. Tumor metabolic rates for glucose (TMRglc) have been shown to vary irrespective of tumor size: in different regions of the same tumor, TMRglc may be substantially higher, equal or lower than in normal brain tissue [34,36,37,39]. PET investigations of human brain tumors revealed that most tumors exhibit slightly lower TMRglc values than normal brain tissue with a trend towards higher values in high-grade malignant tumors [40,41,43,45].…”

Double-resonanceJ-edited1H-NMR detection of [6-13C]-D-2-deoxyglucose uptake in glioma cells

“…However, the latter metabolite cannot react further according to the Embden-Meyerhof pathway, and accumulates in the cell without contributing to the glycolytic fluxes of glucose derivatives. 11 For this reason, isotope-enriched deoxyglucose molecules are currently utilized to detect pathological states by measuring the rate of glucose utilization by brain cells and tissues, [12][13][14] either by autoradiographic techniques in vitro 15 or by PET in vivo. 16 This study demonstrates the effectiveness of T-SEDOR to selectively detect the resonances of protons bound to 13 C of this substrate, while suppressing all signals due to the remaining protons, both in the sugar moiety and in other compounds present in the cells or in the medium.…”