New results
October 07, 2009
A fully automated two-step synthesis of an 18F-labelled tyrosine kinase inhibitor for EGFR kinase activity in tumours
New, very efficient therapeutical agents used in cancer treatments take their effect by inhibiting the signal transduction in tumour cells. However, they are having an effect just in certain sub-groups of patients. The Max Planck Institute’s central research group “Radiochemistry” – led by Bernd Neumaier - developed a new synthesis for a radiotracer which directly addresses the tyrosine kinase deregulation. In this way this tracer may potentially distinguish between drug-sensitive and drug-resistant tumours. Now published in “Applied Radiation and Isotopes”, first results look promising: The PET-based approach provides the opportunity to predict the effectivity of these new therapeutical agents in patients and thus allows a sensible selection of treatment responders.
see also Press Release "A new way to radio labelling"
September 01, 2009
Noradrenergic Modulation of Cortical Networks Engaged in Visuomotor Processing
Both animal and human data suggest that stimulation of the noradrenergic system may influence neuronal excitability in regions engaged in sensory processing and visuospatial attention.
see also Press Release "Getting faster with brain doping"
November 19, 2008
Striatum and pre-SMA facilitate decision-making under time pressure
Human decision-making almost always takes place under time pressure. When people are engaged in activities such as shopping, driving, or playing chess, they have to continually balance the demands for fast decisions against the demands for accurate decisions. In the cognitive sciences, this balance is thought to be modulated by a response threshold, the neural substrate of which is currently subject to speculation. In a speed decision-making experiment, we presented participants with cues that indicated different requirements for response speed. Application of a mathematical model for the behavioral data confirmed that cueing for speed lowered the response threshold. Functional neuroimaging showed that cueing for speed activates the striatum and the pre-supplementary motor area (pre-SMA), brain structures that are part of a closed-loop motor circuit involved in the preparation of voluntary action plans. Moreover, activation in the striatum is known to release the motor system from global inhibition, thereby facilitating faster but possibly premature actions. Finally, the data show that individual variation in the activation of striatum and pre-SMA is selectively associated with individual variation in the amplitude of the adjustments in the response threshold estimated by the mathematical model. These results demonstrate that when people have to make decisions under time pressure their striatum and pre-SMA show increased levels of activation.
see also Press Release "Making decisions.."
October 14, 2008
Noninvasive assessment of E2F-1 mediated transcriptional regulation in vivo
Targeted therapies directed against individual cancer-specific molecular alterations offer the development of disease specific and individualized treatment strategies. Activation of the transcription factor E2F-1 via alteration of the p16- cyclinD- Rb pathway is one of the key molecular events in the development of glioma. Our investigations focused on analyzing the dynamics of the activity of the E2F-1 responsive element under basal conditions and certain stimuli such as chemotherapy using molecular imaging technology. We constructed a retrovirus bearing the Cis-E2F-TA-LUC-IRES-TKGFP reporter system to non-invasively assess E2F-1–dependent transcriptional regulation in culture and in vivo. In summary, non-invasive imaging of E2F-1 as a common downstream regulator of cell cycle progression using the Cis-E2F-TA-LUC-IRES-TKGFP reporter system is highly attractive for evaluating the kinetics of cell cycle regulation and the effects of novel cell cycle targeting anticancer agents in vivo...
- BCNU-induced E2F-1 activity as determined in vivo. E2F-regulated cells and negative and positive control cells were implanted as a set of four tumors in the back of different groups of experimental mice. Mice were followed over time by bioluminescence imaging until tumors could be clearly visualized. Mice were then subjected to BCNU treatment (50%) or control treatment (50%), and repeat imaging was performed 24 h later. An increased luciferase signal was observed only in mice bearing E2F-1-regulated cells and not in mice bearing negative and positive control cells. Color scale, luminescent signal intensity: blue, least intense signal; red, most intense signal.
July 03, 2008
Spreading depolarizations occur in human ischemic stroke with high incidence
Waves of spreading depolarization have often been observed in experimental stroke models. They periodically propagate across cerebral cortex, and the number of waves correlates with infarct size. In collaboration with the Departments of Neurology and Neurosurgery, University of Cologne and the Department of Neurosurgery, University of Heidelberg, we describe now for the first time that similar depolarizations exist in ischemic stroke patients...
see also Press Release
April 22, 2008
Brain scans reveal abnormal activity before human error
According to a new study carried out by Markus Ullsperger from the independent junior research group Cognitive Neurology in collaboration with Tom Eichele from the University of Bergen, Norway, and colleagues from Southampton, Hamburg and Leipzig, individuals conducting monotonous tasks display abnormal brain activity before committing a mistake. Human errors are therefore not solely the result of momentary fluctuations in concentration or brain activity, as has previously been suspected. The results could help predicting upcoming errors and may be a first step to improving safety in the future. The researchers used functional magnetic resonance imaging (fMRI) to scan activity in the brains of subjects engaged in a flanker task, an experiment in which individuals have to quickly respond to visual clues. They found that a set of regions in the brain displayed altered activity up to 30 seconds before a subject made an error. These activated areas included the default mode network region displaying a gradual increase in activity. In brain regions associated with maintaining effort while performing a task a gradual activity decrease was found. Once subjects committed and detected their errors, they re-engaged in the task.
Details on the findings can be found in Eichele et al., Proceedings of the National Academy of Sciences, 2008
- Brain activity preceding errors. Networks of brain regions showing gradually decreasing (upper row) and decreasing (lower row) activity prior to an error.
December 07, 2007
Genetically determined differences in learning from errors
Researchers from the independent junior research group ‚Cognitive Neurology’ and their collaborators in Leipzig, Gießen, and Bonn found that a human genetic polymorphism of the dopamine D2 receptor gene (DRD2 Taq IA) modulates the ability to learn from unfavorable action outcomes.
In a probabilistic learning task, healthy participants with a genotype known to be associated with reduced dopamine D2 receptor density (A1 allele carriers) learned to avoid actions with negative consequences less efficiently. Their posterior frontomedian cortex (pFMC), involved infeedback monitoring, responded less to negative feedback than in others. Dynamically changing interactions between pFMC and hippocampus found to underlie feedback-based learning were reduced in A1-allele carriers. This demonstrates that learning from errors requires dopaminergic signaling. Dopamine D2 receptor reduction seems to decrease sensitivity to negative action consequences.
For full information see Science .
November 21, 2007
Scientists describe the genomic landscape of a human cancer
June 13, 2007
Molecular imaging of inducible gene expression– Switching on the lights for gene therapy
A team of researchers from the laboratory for gene therapy and molecular imaging at the Max-Planck Institute for Neurological Research and the Centre of Molecular Medicine Cologne could recently monitor regulation of gene expression in vivo after viral application by non-invasive imaging technologies like positron emission tomography (PET) and optical imaging (OI). The researchers use a HSV-amplicon vector system expressing PET and OI reporter genes under control of a doxycycline responsive promoter. In the presence of doxycycline expression of the reporter genes is induced and gene expression can be visualised via PET using the PET reporter gene HSV-1 thymidine kinase and the PET tracer 18F-FHBG-PET (figure) or via bioluminescence imaging using the OI reporter gene firefly luciferase. The use of viral vectors bearing reporter and therapeutic genes under control of an inducible promoter may lead to safer application of gene therapy in clinical trials. Read more: PLoS One
November 13, 2006
Multi-modal imaging and imaging-guided gene therapy of experimental glioma
In order to explore gene therapeutic approaches in patients with glioblastoma we use experimental studies. In this context the research group Molecular Imaging could show the feasibility of multi-modal imaging and imaging-guided gene therapy.
In a gene therapeutic approach using the HSV-amplicon vector HSV-cd-IRES-tkgfp we could assess vector mediated transduced tissue dose and gene therapeutic effect with 18F-FHBG- and 18F-FLT-PET respectively (figure). Furthermore, we could demonstrate a positive correlation between transduction efficacy and therapeutic effect. The full data can be found in Cancer Research (Cancer Res 2007; 67: (4) February 15).
