Motor cognition in patients treated with subthalamic nucleus deep brain stimulation: Limits of compensatory overactivity in Parkinson's disease.

Recent fMRI findings revealed that impairment in a serial prediction task in patients suffering from Parkinson's disease (PD) results from hypoactivity of the SMA. Furthermore, hyperactivity of the lateral premotor cortex sustained performance after withdrawal of medication. To further explore these findings, we here examined the impact of deep brain stimulation of the subthalamic nucleus on the activity of the putamen and premotor areas while performing the serial prediction task. To this end, we measured eight male PD patients ON and OFF deep brain stimulation and eight healthy age-matched male controls using [15O] water positron emission tomography to measure regional cerebral blood flow. As expected, PD patients showed poorer performance than healthy controls while performance did not differ between OFF and ON stimulation. Hypoactivity of the putamen and hyperactivity of the left lateral premotor cortex was found in patients compared to controls. Lateral premotor hyperactivity further increased OFF compared to ON stimulation and was positively related to task performance. These results confirm that the motor loop's dysfunction has impact on cognitive processes (here: prediction of serial stimuli) in PD. Extending prior data regarding the role of the lateral premotor cortex in cognitive compensation, our results indicate that lateral premotor cortex hyperactivity, while beneficial in moderate levels of impairment, might fail to preserve performance in more severe stages of the motor loop's degeneration.

Volumetry of [¹¹C]-methionine positron emission tomographic uptake as a prognostic marker before treatment of patients with malignant glioma.

The purpose of this positron emission tomography (PET) study was to compare the prognostic value of pretreatment volume of ¹¹C]-methionine (MET) uptake and semiquantitative MET uptake ratio in patients with malignant glioma. The study population comprised 40 patients with malignant glioma. Pretreatment magnetic resonance imaging (MRI) and MET-PET imaging were performed before the initiation of glioma treatment in all patients. The pretreatment MET uptake ratios and volumes were assessed. To create prognostically homogeneous subgroups, patients' pretreatment prognostic factors were stratified according to the six classes of Radiation Therapy Oncology Group recursive partitioning analysis (RTOG RPA). Univariate and multivariate analyses were performed to determine significant prognostic factors. Survival analyses identified the pretreatment volume of MET uptake and a higher RTOG RPA class as significant predictors. In contrast, pretreatment maximum areas of contrast enhancement on MRI and semiquantitative MET uptake ratios could not be identified as significant prognostic factors. The patients' outcomes and Karnofsky Performance Scale scores were significantly correlated with pretreatment volume of MET uptake but not with semiquantitative MET uptake ratio. The data suggest that pretreatment volumetry of MET uptake but not the semiquantitative MET uptake ratio is a useful biologic prognostic marker in patients with malignant glioma.

11C-Methionine positron emission tomographic imaging of biologic activity of a recurrent glioblastoma treated with stereotaxy-guided laser-induced interstitial thermotherapy.

In patients with recurrent glioblastoma multiforme (GBM), local minimally invasive treatment modalities have gained increasing interest recently because they are associated with fewer side effects than open surgery. For example, local tumor coagulation by laser-induced interstitial thermotherapy (LITT) is such a minimally invasive technique. We monitored the metabolic effects of stereotaxy-guided LITT in a patient with a recurrent GBM using amino acid positron emission tomography (PET). Serial 11C-methyl-L-methionine positron emission tomography (MET-PET) and contrast-enhanced computed tomography (CT) were performed using a hybrid PET/CT system in a patient with recurrent GBM before and after LITT. To monitor the biologic activity of the effects of stereotaxy-guided LITT, a threshold-based volume of interest analysis of the metabolically active tumor volume (MET uptake index of ≥ 1.3) was performed. A continuous decline in metabolically active tumor volume after LITT could be observed. MET-PET seems to be useful for monitoring the short-term therapeutic effects of LITT, especially when patients have been pretreated with a multistep therapeutic regimen. MET-PET seems to be an appropriate tool to monitor and guide experimental LITT regimens and should be studied in a larger patient group to confirm its clinical value.

Imaging of non- or very subtle contrast-enhancing malignant gliomas with [¹¹C]-methionine positron emission tomography.

In patients with World Health Organization (WHO) grade III glioma with a lack of or minimal (< 1 cm3) magnetic resonance imaging (MRI) contrast enhancement, the volume of the metabolically active part of the tumor was assessed by [¹¹C]-methionine positron emission tomography (MET-PET). Eleven patients with WHO grade III gliomas underwent MET-PET and MRI (contrast-enhanced T1- and T2-weighted images). To calculate the volumes in cubic centimeters, threshold-based volume of interest analyses of the metabolically active tumor (MET uptake index ≥ 1.3), contrast enhancement, and the T2 lesion were performed after coregistration of all images. In all patients, the metabolically active tumor volume was larger than the volume of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) enhancement (20.8 ± 18.8 vs 0.29 ± 0.25 cm3; p < .001). With the exception of one patient, the volumes of contrast enhancement were located within the metabolically active tumor volume. In contrast, in the majority of patients, MET uptake overlapped with the T2 lesion and reached beyond it (in 10 of 12 MRIs/MET-PET scans). The present data suggest that in patients with WHO grade III glioma with minimal or a lack of contrast enhancement, MET-PET delineates metabolically active tumor tissue. These findings support the use of combined PET-MRI with radiolabeled amino acids (eg, MET) for the delineating of the true extent of active tumor in the diagnosis and treatment planning of patients with gliomas.

Patient-tailored, imaging-guided, long-term temozolomide chemotherapy in patients with glioblastoma.

We present two patients with glioblastoma with an unusually stable clinical course and long-term survival who were treated after surgery and radiotherapy with adjuvant temozolomide (TMZ) chemotherapy for 17 and 20 cycles, respectively. Afterward, adjuvant TMZ chemotherapy was discontinued in one patient and the dosage of TMZ was reduced in the other. In addition to clinical status and magnetic resonance imaging, the biologic activity of the tumors was monitored by repeated methyl-11C-l-methionine (MET) and 3'-deoxy-3'-18F-fluorothymidine (FLT) positron emission tomography (PET) studies in these patients. In these patients, repeated MET- and FLT-PET imaging documented complete response to the initial treatment regimen, including resection, radiation, and TMZ, and during the course of the disease, recurrent, uncontrollable tumor activity. Continuation or dose escalation of TMZ in both patients was shown to be ineffective to overcome the metabolic activity of the tumor. Our data suggest that repeated MET- and FLT-PET imaging provide information on the biologic activity of a tumor that is highly useful to monitor and detect changes in activity.

Volumetry of [(11)C]-methionine PET uptake and MRI contrast enhancement in patients with recurrent glioblastoma multiforme.

PURPOSE: We investigated the relationship between three-dimensional volumetric data of the metabolically active tumour volume assessed using [(11)C]-methionine positron emission tomography (MET-PET) and the area of gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) enhancement assessed using magnetic resonance imaging (MRI) in patients with recurrent glioblastoma (GBM). MATERIAL AND METHODS: MET-PET and contrast-enhanced MRI with Gd-DTPA were performed in 12 uniformly pretreated patients with recurrent GBM. To calculate the volumes in cubic centimetres, a threshold-based volume-of-interest (VOI) analysis of the metabolically active tumour volume (MET uptake indexes of > or = 1.3 and > or = 1.5) and of the area of Gd-DTPA enhancement was performed after coregistration of all images. RESULTS: In all patients, the metabolically active tumour volume as shown using a MET uptake index of > or = 1.3 was larger than the volume of Gd-DTPA enhancement (30.2 + or - 22.4 vs. 13.7 + or - 10.6 cm(3); p = 0.04). Metabolically active tumour volumes as shown using MET uptake indexes of > or =1.3 and > or = 1.5 and the volumes of Gd-DTPA enhancement showed a positive correlation (r = 0.76, p = 0.003, for an index of > or =1.3, and r = 0.74, p = 0.005, for an index of > or =1.5). CONCLUSION: The present data suggest that in patients with recurrent GBM the metabolically active tumour volume may be substantially underestimated by Gd-DTPA enhancement. The findings support the notion that complementary information derived from MET uptake and Gd-DTPA enhancement may be helpful in developing individualized, patient-tailored therapy strategies in patients with recurrent GBM.

[11C]-L-methionine positron emission tomography in the management of children and young adults with brain tumors.

Only a few Methyl-[11C]-L-methionine (MET) positron emission tomography (PET) studies have focused on children and young adults with brain neoplasm. Due to radiation exposure, long scan acquisition time, and the need for sedation in young children MET-PET studies should be restricted to this group of patients when a decision for further therapy is not possible from routine diagnostic procedures alone, e.g., structural imaging. We investigated the diagnostic accuracy of MET-PET for the differentiation between tumorous and non-tumorous lesions in this group of patients. Forty eight MET-PET scans from 39 patients aged from 2 to 21 years (mean 15 +/- 5.0 years) were analyzed. The MET tumor-uptake relative to a corresponding control region was calculated. A receiver operating characteristic (ROC) was performed to determine the MET-uptake value that best distinguishes tumorous from non-tumorous brain lesions. A differentiation between tumorous (n = 39) and non-tumorous brain lesions (n = 9) was possible at a threshold of 1.48 of relative MET-uptake with a sensitivity of 83% and a specificity of 92%, respectively. A differentiation between high grade malignant lesions (mean MET-uptake = 2.00 +/- 0.46) and low grade tumors (mean MET-uptake = 1.84 +/- 0.31) was not possible. There was a significant difference in MET-uptake between the histologically homogeneous subgroups of astrocytoma WHO grade II and anaplastic astrocytoma WHO grade III (P = 0.02). MET-PET might be a useful tool to differentiate tumorous from non-tumorous lesions in children and young adults when a decision for further therapy is difficult or impossible from routine structural imaging procedures alone.

Perrault Syndrome with progressive nervous system involvement.

A 21-year-old woman with a Perrault Syndrome (PS) presented with progressive ataxia. PS comprises gonadal dysgenesis and sensorineural deafness in females. More recent studies have asked whether the neurologic signs in some of the patients are a coincidental finding or part of the syndrome. Magnetic resonance imaging in PS patients shows high intensity signals in the periventricular and the subcortical white substance, as well as in the centrum ovale, suggestive for cerebral leucodystrophy, which is one of a wide spectrum of neurologic symptoms found in PS. The fluorodeoxyglucose positron emission tomography (PET) of our patient brought results indicating a progressive heredoataxia. PET is helpful in the early detection of the progressive central nervous involvement of PS.

Neuroimaging in patients with gliomas.

Improvements of radionuclide and magnetic resonance-based imaging modalities over the past decade have enabled clinicians to noninvasively assess the dynamics of disease-specific processes at the molecular level in humans. This article will provide an overview of the recent advances in multimodal molecular neuroimaging in patients with primary brain tumors. To date, a range of complementary imaging parameters have been established in the diagnosis of brain tumors. Magnetic resonance imaging (MRI) provides mostly morphological and functional information such as tumor localization, vascular permeability, cell density, and tumor perfusion. The use of positron emission tomography (PET) enables the assessment of molecular processes, such as glucose consumption, expression of nucleoside and amino acid transporters, as well as alterations of DNA and protein synthesis. Taken together, MRI and PET give complementary information about tumor biology and activity, providing an improved understanding about the kinetics of tumor growth.

Molecular imaging-guided gene therapy of gliomas.

Gene therapy of patients with glioblastoma using viral and non-viral vectors, which are applied by direct injection or convection-enhanced delivery (CED), appear to be satisfactorily safe. Up to date, only single patients show a significant therapeutic benefit as deduced from single long-term survivors. Non-invasive imaging by PET for the identification of viable target tissue and for assessment of transduction efficiency shall help to identify patients which might benefit from gene therapy, while non-invasive follow-up on treatment responses allows early and dynamic adaptations of treatment options. Therefore, molecular imaging has a critical impact on the development of standardised gene therapy protocols and on efficient and safe vector applications in humans.

Direct demonstration of transcallosal disinhibition in language networks.

Neuroimaging studies in right-handed patients with left hemisphere brain lesions have demonstrated a shift of language activity from left to right inferior frontal gyrus (IFG). This shift may be caused by greater right hemisphere dominance before the injury or by reduced inhibitory activity of the injured left hemisphere. We simulated a brain lesion applying transcranial -magnetic stimulation over left IFG in normal subjects, while simultaneously measuring language activity with positron -emission tomography. Interference with transcranial -magnetic stimulation decreased activity in left and increased it in right IFG in all subjects. We thus demonstrate for the first time that a rightward shift of language activity is caused by the brain lesion and not by greater right-hemisphere dominance, thus supporting the hypothesis of reduced transcallosal inhibition.

Use of 11C-methionine PET to monitor the effects of temozolomide chemotherapy in malignant gliomas.

PURPOSE: The purpose of this study was to monitor the metabolic effects of temozolomide (TMZ) chemotherapy in malignant gliomas by means of repeated positron emission tomography (PET) with [(11)C]methionine (MET). METHODS: Fifteen patients with histologically proven malignant glioma were treated by TMZ chemotherapy. MET-PET studies were performed before and after the third cycle of TMZ chemotherapy in all patients, and in 12 patients also after the sixth cycle. Gadolinium-enhanced MRI studies were performed in 12 patients before the first and after the sixth cycle. Clinical status was assessed by the modified Rankin scale. Long-term outcome was assessed by calculating the time to progression (TTP) in months. RESULTS: Decline in MET uptake during therapy corresponded to a stable clinical status. The median TTP was significantly longer in patients with decline in MET uptake than in those with increasing MET uptake (23 vs 3.5 months; p=0.01, log rank test). There was no significant correlation between change in MET uptake and change in contrast enhancement during treatment for all patients. CONCLUSION: The present data demonstrate that clinical stability, which is often achieved under TMZ chemotherapy of malignant glioma, corresponds to a decline in or stability of tumour amino acid metabolism. Tumour responses can already be demonstrated with MET-PET after three cycles of chemotherapy, and absence of progression at that time indicates a high probability of further stability during the next three cycles. A reduction in MET uptake during TMZ treatment predicts a favourable clinical outcome. Molecular imaging of amino acid uptake by MET-PET offers a new method of measurement of the biological activity of recurrent glioma.

18F-fluoro-L-thymidine and 11C-methylmethionine as markers of increased transport and proliferation in brain tumors.

UNLABELLED: Because of the high glucose metabolism in normal brain tissue 18F-FDG is not the ideal tracer for the detection of gliomas. Methyl-11C-l-methionine (11C-MET) is better suited for imaging the extent of gliomas, because it is transported specifically into tumors but only insignificantly into normal brain. 3'-Deoxy-3'-18F-fluorothymidine (18F-FLT) has been introduced as a proliferation marker in a variety of neoplasias and has promising potential for the detection of brain tumors, because its uptake in normal brain is low. Additionally, the longer half-life might permit differentiation between transport and intracellular phosphorylation. METHODS: PET of 18F-FLT and 11C-MET was performed on 23 patients (age range, 20-70 y) with histologically verified gliomas of different grades. On all patients, conventional MRI was performed, and 16 patients additionally underwent contrast-enhanced imaging. Images were coregistered, and the volumes of abnormality were defined for PET and MRI. Uptake ratios and standardized uptake values (SUVs) of various tumors and regions were assessed by region-of-interest analysis. Kinetic modeling was performed on 14 patients for regional time-activity curves of 18F-FLT from tumorous and normal brain tissue. RESULTS: Sensitivity for the detection of tumors was lower for 18F-FLT than for 11C-MET (78.3% vs. 91.3%), especially for low-grade astrocytomas. Tumor volumes detected by 18F-FLT and 11C-MET were larger than tumor regions displaying gadolinium enhancement (P<0.01). Uptake ratios of 18F-FLT were higher than uptake ratios of 11C-MET (P<0.01). Uptake ratios of 18F-FLT were higher in glioblastomas than in astrocytomas (P<0.01). Absolute radiotracer uptake of 18F-FLT was low and significantly lower than that of 11C-MET (SUV, 1.3+/-0.7 vs. 3.1+/-1.0; P<0.01). Some tumor regions were detected only by either 18F-FLT (7 patients) or 11C-MET (13 patients). Kinetic modeling revealed that 18F-FLT uptake in tumor tissue seems to be predominantly due to elevated transport and net influx. However, a moderate correlation was found between uptake ratio and phosphorylation rate k3 (r=0.65 and P=0.01 for grade II-IV gliomas; r=0.76 and P<0.01 for grade III-IV tumors). CONCLUSION: 18F-FLT is a promising tracer for the detection and characterization of primary central nervous system tumors and might help to differentiate between low- and high-grade gliomas. 18F-FLT uptake is mainly due to increased transport, but irreversible incorporation by phosphorylation might also contribute. In some tumors and tumor areas, 18F-FLT uptake is not related to 11C-MET uptake. In view of the high sensitivity and specificity of 11C-MET PET for imaging of gliomas, it cannot be excluded that 18F-FLT PET was false positive in these areas. However, the discrepancies observed for the various imaging modalities (18F-FLT and 11C-MET PET as well as gadolinium-enhanced MRI) yield complementary information on the activity and the extent of gliomas and might improve early evaluation of treatment effects, especially in patients with high-grade gliomas. Further studies are needed, including coregistered histology and kinetic analysis in patients undergoing chemotherapy.

Imaging in neurooncology.

Imaging in patients with brain tumors aims toward the determination of the localization, extend, type, and malignancy of the tumor. Imaging is being used for primary diagnosis, planning of treatment including placement of stereotaxic biopsy, resection, radiation, guided application of experimental therapeutics, and delineation of tumor from functionally important neuronal tissue. After treatment, imaging is being used to quantify the treatment response and the extent of residual tumor. At follow-up, imaging helps to determine tumor progression and to differentiate recurrent tumor growth from treatment-induced tissue changes, such as radiation necrosis. A variety of complementary imaging methods are currently being used to obtain all the information necessary to achieve the above mentioned goals. Computed tomography and magnetic resonance imaging (MRI) reveal mostly anatomical information on the tumor, whereas magnetic resonance spectroscopy and positron emission tomography (PET) give important information on the metabolic state and molecular events within the tumor. Functional MRI and functional PET, in combination with electrophysiological methods like transcranial magnetic stimulation, are being used to delineate functionally important neuronal tissue, which has to be preserved from treatment-induced damage, as well as to gather information on tumor-induced brain plasticity. In addition, optical imaging devices have been implemented in the past few years for the development of new therapeutics, especially in experimental glioma models. In summary, imaging in patients with brain tumors plays a central role in the management of the disease and in the development of improved imaging-guided therapies.

Delineation of brain tumor extent with [11C]L-methionine positron emission tomography: local comparison with stereotactic histopathology.

PURPOSE: Methyl-[11C]L-methionine ([11C]MET) positron emission tomography (PET) in brain tumors reflects amino acid transport and has been shown to be more sensitive than magnetic resonance imaging in stereotactic biopsy planning. It remains unclear whether the increased [11C]MET uptake is limited to solid tumor tissue or even detects infiltrating tumor parts. EXPERIMENTAL DESIGN: In 30 patients, a primary or recurrent brain tumor was suspected on magnetic resonance imaging. Patients were investigated with [11C]MET-PET before stereotactic biopsy. The biopsy trajectories were plotted into the [11C]MET-PET images with a newly designed C-based software program. The exact local [11C]MET uptake was determined within rectangular regions of interest of 4 mm in width and length aligned with the biopsy specimen. Individual histologic specimens were rated for the presence of solid tumor tissue, infiltration area, and nontumorous tissue changes. RESULTS: Receiver operating characteristics analysis demonstrated a sensitivity of 87% and specificity of 89% for the detection of tumor tissue at a threshold of 1.3-fold [11C]MET uptake relative to normal brain tissue. At this threshold, only 13 of 100 tumor positive specimen were false negative mainly in grade 2 astrocytoma. In grade 2 astrocytoma, mean [11C]MET uptake in the infiltration area was significantly higher than in solid tumor tissue (P < 0.003). CONCLUSIONS: [11C]MET-PET detects solid parts of brain tumors, as well as the infiltration area at high sensitivity and specificity. High [11C]MET uptake in infiltrating tumor of astrocytoma WHO grade 2 reflects high activity in this tumor compartment. Molecular imaging, with [11C]MET, will guide improved management of patients with brain tumors.

Probability of cortical infarction predicted by flumazenil binding and diffusion-weighted imaging signal intensity: a comparative positron emission tomography/magnetic resonance imaging study in early ischemic stroke.

BACKGROUND AND PURPOSE: The differentiation of reversible from irreversible ischemic damage is essential for identifying patients with acute ischemic deficits who may benefit from therapeutic interventions. Diffusion-weighted imaging (DWI) has become the method of choice to detect ischemic lesions. Positron emission tomography (PET) of the central benzodiazepine receptor ligand 11C flumazenil (FMZ) has been shown to be a reliable marker of neuronal integrity. These 2 imaging parameters were compared with respect to the probability to predict cortical infarction in early ischemic stroke. METHODS: In 12 patients with acute stroke, results from DWI (median, 6.5 hours after symptom onset) and FMZ-PET (interval, 85 minutes between DWI and PET) were compared with infarct extension 24 to 48 hours after onset of stroke on T2-weighted magnetic resonance imaging (T2-MRI). Probability curves predictive of eventual infarction were computed using respective DWI, FMZ, and apparent diffusion coefficient (ADC) values for voxels of interest (VOI) later classified as representing infarcted or noninfarcted tissue. RESULTS: Ninety-five percent limits predictive of cortical infarction were determined for relative FMZ binding (< or =3.2), DWI signal intensity (> or =1.18), and ADC values (< or =0.83). Cortical regions with values beyond these 95% limits did not necessarily overlap with nor were fully congruous with final cortical infarct volumes. The respective median volumes for these regions were FMZ median 10.9, range 0 to 99.7 cm3; DWI median 15.2, range 0 to 116.0 cm3; ADC median 12.4, range 0 to 112.7 cm3; and final infarct median 14.9, range 0 to 114.7 cm(3). Overall, 83.5% of the final infarct, on average, was predicted by decreased FMZ binding, 84.7% by increased DWI signal intensity, and 70.9% by a decreased ADC value. The portions of the final infarct not predicted in the early investigation (false-negatives) were 4.8 cm3 (median) for FMZ, 3.7 cm3 for DWI, and 6.0 cm3 for ADC. The false-positive volumes not included in the final infarct were 0 cm3 (median) for FMZ, 5.1 cm3 for DWI, and 3.6 cm3 for ADC. CONCLUSIONS: These results indicate that FMZ-PET and DWI are comparable in the prediction of probability of ischemic cortical infarction, but FMZ-PET carries a lower probability of false-positive prediction. The final infarcts include tissue not identified by these imaging modalities; at the time of the study, these tissue compartments are viable and could benefit from treatment. The discrepancy in predictive probability could be related to the fundamental difference of the measured variables: benzodiazepine receptor activity is a reliable marker of neuronal integrity in the cortex, and movement of water molecules in the extracellular space might be a more variable indicator of tissue damage.

Organic and psychogenic factors leading to executive dysfunctions in a patient suffering from surgery of a colloid cyst of the Foramen of Monro.

The authors report a 41-year-old female patient who had suffered from colloid cyst of the Foramen of Monro. After surgical intervention in which the cyst was completely removed, her hydrocephalus decreased to normal ventricle size measured by MRI. However, the patient became depressive and reported vast difficulties in everyday life decision-making. An examination twenty months after surgery indicated psychiatric symptoms and abnormalities in personality. Neuropsychological investigation revealed average to above average performance in anterograde memory, attention, information processing, and intelligence. In contrast, the patient was severely impaired in decision-making, complex executive functions, and social cognition. In 18F-2-fluoro-2-deoxy-D-glucose (18FDG-PET) hypometabolism in bilateral dorsolateral prefrontal cortex, cingulate cortex and left fusiform gyrus was observed. The authors conclude that in this case decision-making deficits and executive dysfunctions are influenced by both organic and psychogenic factors.

Methyl-[11C]- l-methionine uptake as measured by positron emission tomography correlates to microvessel density in patients with glioma.

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.