Glucose Transport across the Blood—Brain Barrier in Normal Human Subjects and Patients with Cerebral Tumours Studied Using [¹¹C]3-O-Methyl-D-Glucose and Positron Emission Tomography

Abstract

Summary:The kinetics of the regional cerebral uptake of ["C] 3-0-methyl-o-glucose (["C1MeG), a competitive in hibitor of o-glucose transport, have been studied in normal human subjects and patients with cerebral tu mours using positron emission tomography (PET), Con comitant measurement of regional cerebral blood volume and blood flow enabled corrections for the contribution of intravascular tracer signal in PET scans to be carried out and regional unidirectional cerebral ["C1MeG extrac tions to be determined, A three-compartment model con taining an arterial plasma and two cerebral compartments was required to produce satisfactory fits to experimental regional cerebral [ l lCJMeG uptake data. Under fasting, resting conditions, normal controls had mean unidirec tional whole-brain, cortical, and white matter ["C1MeG extractions of 14, 13, and 17%, respectively. Mean values of k, and k2, first-order rate constants describing forward and back transport, respectively, of tracer into the first cerebral compartment, were similar for ["C1 MeG and ['8F] 2-fluoro-2-deoxy-o-glucose ( , 8FDG), a second comStudies on intact dog and rat brain, and also on isolated cerebral rat brain capillaries, have shown that D-glucose transport across the blood-brain barrier (BBB) is a passive facilitated process (Crone, 1965; Betz et aI., 1973 Betz et aI., , 1979 Pard ridge and Oldendorf, 1975). 3-0-Methyl-D-glucose (MeG) and 2-deoxY-D-glucose (2-DG) have both been shown to

Assessment of insulin sensitivity in vivo in control and diabetic mice with a radioactive tracer of glucose transport: [125I]‐6‐deoxy‐6‐iodo‐D‐glucose

“…6-DIG will be of clinical interest only if it can be used to identify variations in glucose transport in vivo, as demonstrated with 3-OMG. In fact, [ 11 C]-3-OMG has been used with dynamic positron emission tomography (PET) to study variations in glucose transport in cardiology [21] and neurology [22,[38][39][40]. However, more recently, Bonadonna et al have used carbon 14-labelled 3-OMG in vivo to identify insulin resistance in the skeletal muscle of patients with type 2 diabetes [1].…”

Glycolytic glioma cells with active glycogen synthase are sensitive to PTEN and inhibitors of PI3K and gluconeogenesis

“…The resilience of malignant gliomas to anaerobic conditions suggests that their potential for glycolysis is increased. [5][6][7] Large amounts of glucose can be transported into glioma cells for glycolysis and increased glucose extraction within the tumors 8 is accommodated by increased expression of GLUT3 transporters. [9][10][11] Maintaining increased levels of hypoxia-inducible factor-1a (HIF1a) is one mechanism that induces glycolytic enzyme expression.…”

The applications of positron emission tomography to oncology

“…These data indicate that even in cases where there is a plentiful supply of blood and, hence, oxygen, the tumour often has only a modest demand for this supply. It has also been demonstrated by Patronas et al (1982) and Brooks et al (1986) (Knopp et al, 1990) reductions in glucose metabolism of lung tumours responding to radio-or chemotherapy. Alavi et al (1988) have measured a strong correlation between initial glucose metabolism and prognosis for patients with primary cerebral tumours, the result appearing stronger than that predicted by a simple histological grading system.…”