[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

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

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).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.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).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

The Inflammatory Kinase MAP4K4 Promotes Reactivation of Kaposi's Sarcoma Herpesvirus and Enhances the Invasiveness of Infected Endothelial Cells

Kaposi's sarcoma (KS) is a mesenchymal tumour, which is caused by Kaposi's sarcoma herpesvirus (KSHV) and develops under inflammatory conditions. KSHV-infected endothelial spindle cells, the neoplastic cells in KS, show increased invasiveness, attributed to the elevated expression of metalloproteinases (MMPs) and cyclooxygenase-2 (COX-2). The majority of these spindle cells harbour latent KSHV genomes, while a minority undergoes lytic reactivation with subsequent production of new virions and viral or cellular chemo- and cytokines, which may promote tumour invasion and dissemination. In order to better understand KSHV pathogenesis, we investigated cellular mechanisms underlying the lytic reactivation of KSHV. Using a combination of small molecule library screening and siRNA silencing we found a STE20 kinase family member, MAP4K4, to be involved in KSHV reactivation from latency and to contribute to the invasive phenotype of KSHV-infected endothelial cells by regulating COX-2, MMP-7, and MMP-13 expression. This kinase is also highly expressed in KS spindle cells in vivo. These findings suggest that MAP4K4, a known mediator of inflammation, is involved in KS aetiology by regulating KSHV lytic reactivation, expression of MMPs and COX-2, and, thereby modulating invasiveness of KSHV-infected endothelial cells. © 2013 Haas et al

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

Brand M, Kalbe E, Kracht LW, et al. Organic and psychogenic factors leading to executive dysfunctions in a patient suffering from surgery of a colloid cyst of the Foramen of Monro. NEUROCASE. 2004;10(6):420-425.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 F-18-2-fluoro-2-deoxy-D-glucose ((18)FDG-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