scholarly journals 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

1986 ◽  
Vol 6 (2) ◽  
pp. 230-239 ◽  
Author(s):  
D. J. Brooks ◽  
R. P. Beaney ◽  
A. A. Lammertsma ◽  
S. Herold ◽  
D. R. Turton ◽  
...  

The kinetics of the regional cerebral uptake of [11C]3- O-methyl-d-glucose ([11C]MeG), a competitive inhibitor of d-glucose transport, have been studied in normal human subjects and patients with cerebral tumours using positron emission tomography (PET). Concomitant 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 [11C]MeG extractions to be determined. A three-compartment model containing an arterial plasma and two cerebral compartments was required to produce satisfactory fits to experimental regional cerebral [11C]MeG uptake data. Under fasting, resting conditions, normal controls had mean unidirectional whole-brain, cortical, and white matter [11C]MeG extractions of 14, 13, and 17%, respectively. Mean values of k1 and k2, first-order rate constants describing forward and back transport, respectively, of tracer into the first cerebral compartment, were similar for [11C]MeG and [18F]2-fluoro-2-deoxy-d-glucose (18FDG), a second competitive inhibitor of d-glucose transport, k3, a rate constant describing FDG phosphorylation, was 20 times higher for cortical FDG uptake than the k3 fitted for [11C]MeG cortical uptake. Glioma [11C]MeG extractions ranged from normal levels of 12% to raised levels of 30%. Transport of [11C]MeG in and out of contralateral cortical tissue was significantly depressed in patients with gliomas. It is concluded that under fasting, resting conditions, regional cerebral glucose extraction remains relatively uniform throughout normal brain tissue. Gliomas, however, may have raised levels of glucose extraction. The nature of the second cerebral compartment required to describe [11C]MeG uptake is unclear, but it could represent either a useless phosphorylation–dephosphorylation cycle or nonspecific tracer uptake by a cerebral sub-compartment.

1984 ◽  
Vol 4 (3) ◽  
pp. 458-465 ◽  
Author(s):  
David J. Brooks ◽  
Adriaan A. Lammertsma ◽  
Ronald P. Beaney ◽  
Klaus L. Leenders ◽  
Peter D. Buckingham ◽  
...  

The cerebral pH of four normal human subjects has been measured using continuous inhalation of 11CO2 and positron emission tomography (PET). 11CO2 was administered to each subject at a constant rate for 15 min, during which time serial arterial plasma 11C levels were determined and serial 11C cerebral uptake PET scans were performed at a fixed axial tomographic level. 11C uptake kinetics were analysed using a three-compartment model. Rate constants have been estimated for the free exchange of 11CO2 between plasma and cerebral compartments for each subject, and their cerebral pH calculated. Whole brain pH values ranged from 6.96 to 7.05, and no significant pH difference between regions containing predominantly grey or white matter was noted. Best fits to 11C uptake data were achieved by effectively neglecting the metabolic fixation of 11C by cerebral tissue. The purpose of this study was to test the feasibility of pH measurement using the 11CO2 continuous inhalation technique. It is concluded from the results and the error analysis that continuous 11CO2 inhalation combined with PET is potentially a simple and useful method for determining regional cerebral pH.


1987 ◽  
Vol 28 (6) ◽  
pp. 673-681 ◽  
Author(s):  
M. Mosskin ◽  
H. von Holst ◽  
M. Bergström ◽  
V. P. Collins ◽  
L. Eriksson ◽  
...  

A selected group of 36 patients with suspected supratentorial gliomas were investigated with positron emission tomography (PET) using 11C-methionine and transmission computed tomography (CT) before and after intravenous injection of contrast medium. Every examination was performed with the head fixed in a plastic helmet and a baseplate to guarantee that the slice orientation was the same at examinations with the two modalities and over time. Guided by the examinations, multiple stereotactic biopsies were performed with the biopsy instrument mounted on the baseplate. Regional accumulation of methionine was compared with histology of the corresponding samples and with attenuation before and after injection of contrast medium as well as mass effect on CT. Typically, there was a low attenuating lesion with a slight mass effect on CT. There was an increased accumulation compared with normal brain tissue in 31 cases of tumours and ordinary or decreased accumulation in 3 cases of tumours. In 22 cases with increased accumulation of methionine the extension of the tumour judged by PET corresponded with that of histology. In 4 cases tumour cells were found outside the area with pathologic methionine uptake. In 5 patients there were areas with increased methionine accumulation where no tumour cells were found. In 22 cases PET using methionine was more accurate than CT in defining the tumour boundaries as determined from the histologic findings. Four groups of biopsy specimens with different amounts of methionine accumulation are described. The uptake in a single biopsy gives good but not exact information about the histology of the specimen.


Synapse ◽  
2002 ◽  
Vol 45 (2) ◽  
pp. 105-112 ◽  
Author(s):  
Gwenn S. Smith ◽  
Yilong Ma ◽  
Vijay Dhawan ◽  
Handan Gunduz ◽  
Maren Carbon ◽  
...  

1984 ◽  
Vol 4 (3) ◽  
pp. 317-322 ◽  
Author(s):  
Adriaan A. Lammertsma ◽  
David J. Brooks ◽  
Ronald P. Beaney ◽  
David R. Turton ◽  
Malcolm J. Kensett ◽  
...  

A method is described for measuring the regional cerebral-to-large vessel haematocrit ratio using inhalation of carbon-11-labelled carbon monoxide and the intravenous injection of carbon-11-labelled methyl-albumin in combination with positron emission tomography. The mean value in a series of nine subjects was 0.69. This is ∼20% lower than the value of 0.85 previously reported. It is concluded that previous measurements of regional cerebral blood volume using a haematocrit ratio of 0.85 will have underestimated the value of regional cerebral blood volume by 20%.


1993 ◽  
Vol 13 (5) ◽  
pp. 733-747 ◽  
Author(s):  
Robert P. Quarles ◽  
Mark A. Mintun ◽  
Kenneth B. Larson ◽  
Joanne Markham ◽  
Ann Mary MacLeod ◽  
...  

To further our understanding of the best way to measure regional CBF with positron emission tomography (PET), we directly compared two candidate tracers ([15O]water and [11C]butanol, administered intravenously) and two popular implementations of the one-compartment (IC) model: the autoradiographic implementation representing a single PET measurement of tissue radioactivity over 1 min and a dynamic implementation representing a sequence of measurements of tissue radioactivity over 200 s. We also examined the feasibility of implementing a more realistic, and thus more complex, distributed-parameter (DP) model by assigning fixed values for all of its parameters other than CBF and tracer volume of distribution ( Vd), a requirement imposed by the low temporal resolution and statistical quality of PET data. The studies were performed in three normal adult human subjects during paired rest and visual stimulation. In each subject seven regions of interest (ROIs) were selected, one of which was the primary visual cortex. The corresponding ROI were anatomically equivalent in the three subjects. Regional CBF, Vd, tracer arrival delay, and dispersion were estimated for the dynamic data curves. A total of 252 parameter sets were estimated. With [11C]butanol both implementations of the IC model provided similar results ( r = 0.97). Flows estimated using the 1C models were lower (p < 0.01) with [15O]water than with [11C]butanol. In comparison with the IC model, the constrained version of the DP used in these studies performed inadequately, overestimating high flow and underestimating low flow with both tracers, possibly as the result of the necessity of assigning fixed values for all of its parameters other than CBF and Vd.


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