RELATIONSHIPS AMONG LACTATE CONCENTRATION, BLOOD-FLOW AND HISTOPATHOLOGIC PROFILES IN RAT C6 GLIOMA

Increased capacity for glycolytic metabolism is a well-known character istic of neoplastic cells. Because lactic acid is the end product of g lycolysis, in vivo MRS measurements of tumor lactate concentration ([l ac](t)) may provide valuable information about tumor metabolism, which will aid the development of therapies and the clinical diagnosis and treatment of tumors. In the present study, several hemodynamic and his tologic parameters were evaluated with respect to their influence on [ lac](t). Pronounced differences in [lac](t) in two distinct population s of tumors suggested a putative perfusion threshold. Above this thres hold, [lac](t) was independent of hemodynamic and histologic factors i ncluding tumor blood flow (measured using MRS and the method of D2O wa shout), extent of necrosis and inflammatory cell infiltrate. Thus, for most tumors, [lac](t) was not determined by any one single factor suc h as hypoxia, venous clearance, glucose supply, extent of necrosis or degree of inflammatory cell infiltrate. Rather, [lac](t) may be equili brated, at least in part, by an interplay of forces involving hemodyna mics and substrate supply. In general, the data are consistent with th e hypothesis that elevated lactate in most tumors is related to the hi gh glycolytic activity of adequately perfused, viable neoplastic cells .