Management of low-grade gliomas continues to be a challenging task, because CT and MRI do not always differentiate from nontumoral lesions. Furthermore, tumor extent and aggressiveness often remain unclear because of a lack of contrast enhancement. Previous studies indicated that large neutral amino acid tracers accumulate in most brain tumors, including low-grade gliomas, probably because of changes of endothelial and blood-brain barrier function. We describe 11C-methionine uptake measured with PET in a series of 196 consecutive patients, most of whom were studied because of suspected low-grade gliomas. Uptake in the most active lesion area, relative to contralateral side, was significantly different among high-grade gliomas, low-grade gliomas, and chronic or subacute nontumoral lesions, and this difference was independent from contrast enhancement in CT or MRI. Corticosteroids had no significant effect on methionine uptake in low-grade gliomas but reduced uptake moderately in high-grade gliomas. Differentiation between gliomas and nontumoral lesions by a simple threshold was correct in 79%. Recurrent or residual tumors had a higher uptake than primary gliomas. In conclusion, the high sensitivity of 11C-methionine uptake for functional endothelial or blood-brain barrier changes suggests that this tracer is particularly useful for evaluation and follow-up of low-grade gliomas.

No abstract

Positron emission tomography (PET) using methyl-[(11)C]- l-methionine ([(11)C]MET) is a useful tool in the diagnosis of brain tumours. The main mechanism of [(11)C]MET uptake is probably increased transport via the L-transporter system located in the endothelial cell membrane. We used [(11)C]MET-PET and microvessel count in glioma specimens to investigate whether the increased amino acid uptake is related to angiogenesis. Twenty-one patients with newly diagnosed and histologically confirmed glioma were investigated with [(11)C]MET-PET before open surgery. [(11)C]MET uptake was determined within an 8-mm region of interest in the area of the tumour showing the highest uptake, and the ratio to uptake in the corresponding contralateral region was calculated. To measure angiogenesis, immunostaining with factor VIII antibody was applied to sections from tumour tissue, and highlighted microvessels were counted in the area of highest vascularisation. In the entire patient group, a positive correlation was found between microvessel count and [(11)C]MET uptake (Spearman: r=0.89, P<0.001). This correlation was also significant in subgroups of patients [patients with grade II and III astrocytomas (Spearman: r=0.77, P<0.01) and patients with glioblastoma (Spearman: r=0.64, P<0.05)]. Angiogenesis, as assessed by microvessel count, and increased amino acid uptake, as assessed by [(11)C]MET-PET, are closely related events in gliomas. [(11)C]MET-PET offers a direct measure of amino acid transport and an indirect measure of microvessel density. [(11)C]MET-PET might be a useful tool to select potential responders to anti-angiogenic therapy and to monitor patients during such therapy.

Background and Purpose-Central benzodiazepine receptor ligands, such as [11 C]flumazenil (FMZ), are markers of neuronal integrity and therefore might be useful in the differentiation of functionally and morphologically damaged tissue early in ischemic stroke. We sought to assess the value of a benzodiazepine receptor ligand for the early identification of irreversible ischemic damage to cortical areas that cannot benefit from reperfusion. Methods-Eleven patients (7 male, 4 female, aged 52 to 75 years) with acute, hemispheric ischemic stroke were treated with alteplase (recombinant tissue plasminogen activator; 0.9 mg/kg according to National Institute of Neurological Disorders and Stroke protocol) within 3 hours of onset of symptoms. At the beginning of thrombolysis, cortical cerebral blood flow ([ 15 O]H 2 O) and FMZ binding were assessed by positron emission tomography (PET). Those early PET findings were related to the change in neurological deficit (National Institutes of Health Stroke Scale) and to the extent of cortical damage on MRI or CT 3 weeks after the stroke. Results-Hypoperfusion was observed in all cases, and in 8 patients the values were below critical thresholds estimated at 12 mL/100 g per minute, comprising 1 to 174 cm 3 of cortical tissue. Substantial reperfusion was seen in most of these regions 24 hours after thrombolysis. In 4 cases, distinct areas of decreased FMZ binding were detected. Those patients suffered permanent lesions in cortical areas corresponding to their FMZ defects (112 versus 146, 3 versus 3, 2 versus 1, and 128 versus 136 cm 3 ). In the other patients no morphological defects were detected on MRI or CT, although blood flow was critically decreased in areas ranging in size up to 78 cm 3 before thrombolysis. Conclusions-These findings suggest that imaging of benzodiazepine receptors by FMZ PET distinguishes between irreversibly damaged and viable penumbra tissue early after acute stroke. (Stroke. 2000;31:366-369.)

No abstract