Anna BrГјggemann

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I also want to say thanks to the companies who are supporting this meeting and the MI community; especially to those who come to Warszawa.

Do not forget that Warszawa is a lively city, with a number of historical sites, museums and parks. We are also in the year of Chopin; you can find a lot of information about his music and places he used to live.

Take some time to immerse yourself in the history of the city. On behalf of local organizing committee I wish your visit to Warszawa will be informative, interesting and enjoyable.

In my capacity as president of the European Society of Radiology I would like to thank the organisers of this important event that has been organised in close cooperation with the ESR for their kind invitation.

It is an honour to be here today as the ESR has supported the creation of the European Society for Molecular Imaging from the very beginning and many ESR representatives have been and are still represented in this organisation.

We are looking forward to enhancing the successful cooperation between the European Society for Molecular Imaging and the European Society of Radiology in the future.

Realising the importance of molecular imaging, latest research discoveries in this field and possible translations into medical practice, I will reinforce the topic of molecular imaging within the European Society of Radiology during my presidency and make sure that the work of all ESR bodies is coordinated with a special focus on this issue.

The ESR would be most happy to welcome you at its annual meeting. I thank you for having taken the time to be with us in Warsaw this week and I wish you a most successful meeting.

Sincerely, Professor Maximilian F. How to get there Warsaw, the capital of Poland, a captivating city with a distinctive atmosphere and definitely worth visiting.

Warsaw is a perfect embodiment of changes that have taken place in Poland in the past 20 years. Whether you come to Warsaw on a business trip, for a conference, or as a tourist, Warsaw will definitely exceed your expectations.

From Warszawa Centralna railway station take tram No. Via the E30, E77 or E67 highways, head in the direction of Centrum.

By metro, alight at Centrum. Zamojski Palace is within walking distance. Looking forward to meeting you there. Close to the iconic Palace of Culture and Science and m from the railway station with a convenient connection to the airport.

GEHC 2. ART 3. CaliperLS 6. MR solutions 7. Carestream 8. LOT-Oriel CT Imaging VisEn LI-COR Polatom This meeting would not have been possible without your support.

For full list, visit our website. Contag Dr. Contag received his B. Paul in ; and earned his Ph. He was a postdoctoral fellow at Stanford University from , and joined the faculty in Pediatrics at Stanford in with a joint appointment in Microbiology and Immunology and a courtesy appointment in Radiology.

Contag is a pioneer in the emerging field of molecular imaging and is developing imaging approaches aimed at revealing molecular processes in living subjects and advancing therapeutic strategies through imaging.

His laboratory develops macroscopic and microscopic optical imaging tools and uses imaging to assess tissue responses to stress, reveal immune cell migration patterns, understand stem cell biology and advance biological therapies.

He is a founding member, and a past president, of the Society for Molecular Imaging, and for his fundamental contributions in imaging, is a recipient of the Achievement Award from the Society for Molecular Imaging.

Contag is a scientific founder of Xenogen Corp. He is also a founder of ConcentRx Corp. Heme Oxygenase-1 Deficiency leads to disrupted response to acute stress in stem cells and progenitors.

Chemical control of protein stability and function in living mice. Nature Med. Real-time analysis of uptake and bioactivatable cleavage of luciferin-transporter conjugates in transgenic reporter mice.

Synergistic antitumor effects of immune cell-viral biotherapy. Shifting foci of hematopoeisis during reconstitution from single stem cells.

Extracellular replication of Listeria monocytogenes in the gall bladder. The writing is on the vessel wall. MYC inactivation uncovers stem cell properties and induces the state of tumor dormancy in hepatocellular cancer.

Nature, Bioluminescent indicators in living mammals. There are technological and translathe body to interrogate disease states microscopi- tional advances that are driving this field and are cally.

This is leading to an emerging field of in vivo leading towards in vivo microscopy becoming a stanpathology that is changing the diagnostic para- dard clinical tool.

By removing the spatiotemporal digm from biopsy separation between the pathologist and patient, we and conventional can accelerate clinical diagnosis and advance clinihistopathology to cal care for patients with a wide variety of diseases.

These advances are clos- References ing the gap between the patient and the 1. While recent advances in this image guidance during brain surgery.

In Press. IEEE J. Topics Quantum Electronics. J Biomed Optics 14, J Biomed Opt. Sci, USA. She was then assistant lecturer and subsequently moved to the University of Liverpool as a Post-doctoral Research Fellow.

In , she obtained a prestigious David Phillips Fellowship, to develop her work on intracellular signalling dynamics. She is focusing on the imaging of single living cells in order to understand regulation of gene transcription and cell fate.

She has recently been interested in using new techniques for single molecule imaging in live cells based on the use of gold nanoparticles.

Science , See, V. The Journal of cell biology , Nelson, D. Biochemical Society transactions 32, Ashall, L. ACS nano 3, Meley, D.

In most cases, oscillations had previously been masked in population level studies by cellular heterogeneity. We have also observed cell to cell heterogeneity in other signalling systems such as in cellular response to low oxygen environment hypoxia.

In both inflammatory and hypoxic signalling systems one source of heterogeneity is due to the presence of extrinsic dynamic processes that are functionally coupled and that are occurring over different time scales.

We identified the cell cycle as one source of variability as cells must coordinate and prioritise their response to the environment depending on their cell cycle status.

We apply mathematical modelling using the quantitative data generated by imaging experiments to predict the role of the negative feedback, to unravel new network motifs and to characterise the cross-talk between the signalling systems.

The scientific focus of our lab is on the mechanisms that regulate cell-cell interactions during scenarios, such as arterial or venous thrombosis, stem cell homing and differentiation, during inflammation as well as in cancer development and progression.

To evaluate the interaction between different cell subsets in their physiological micro- environment, we have established novel imaging approaches that allow dissecting all the steps involved both in reductionist in vitro assays and in vivo.

The in vivo approaches are complemented by sophisticated in vitro assays allowing investigation of cell-cell interactions on a subcellular and molecular level.

The multimodal imaging approaches will contribute to a better understanding of the molecular mechanisms and the kinetic aspects of the dynamic process of cell-cell interactions under physiological conditions and in the disease states.

However, there are several challenges for the efficient evaluation of these drugs in clinical trials as well as for the use in clinical practice.

These include i the selection of patients likely to benefit from treatment with a specific targeted drug, ii finding the right dose and dose schedule, iii monitoring target inhibition, and Standard anatomic imaging continues to play an important role for addressing these challenges, but molecular imaging provides several new opportunities to make the use of targeted drugs more efficient.

Using molecular imaging the expression of drug targets can be assessed non-invasively, the concentration of drugs can be measured in the tumor tissue, target inhibition can be monitored and tumor response to therapy can be evaluated earlier than with anatomic imaging techniques.

Therefore it is expected that molecular imaging will play an increasing role for guiding molecularly defined therapeutic interventions.

Methods: Quantitative anatomical, molecular, and functional characteristics can be used as imaging biomarkers.

However, they are not early biomarkers and are limited in the assessment of some tumors and targeted treatments. The use of molecular imaging biomarkers is restricted by their narrow target specificity and by the complexity of the biology in tumors.

In a given tumor type, several different subgroups often exist with overexpression of different proteins and signaling pathways. The rationale of this approach is that most cancers have acquired the same functional capabilities including upregulated glycolysis, limitless proliferation, extensive angiogenesis, resistance to apoptosis and metastasis formation.

Conclusions: Functional biomarkers have an important potential to help in selecting the patients and assessing the response to new treatments, especially in phase 1 and 2 clinical trials.

However, important efforts of validation and standardization remain to be done before the wide use of functional biomarkers and their acceptance as surrogate endpoints that can replace clinical endpoints such as survival or time to progression.

Therefore, it is often preferred to assess downstream changes of molecular pathways with functional References: 1.

The hallmarks of cancer. Rudin M. Imaging readouts as biomarkers or surrogate parameters for the assessment of therapeutic interventions.

Eur Radiol. Diffusion-weighted magnetic resonance imaging as a cancer biomarker. Biomarkers in abdominal imaging.

Abdom Imaging. Besides therapeutic agents, they are also effective as a diagnostic tool for targeted imaging when labeled with a suitable radionuclide[1].

After production, a number of candidate binders are obtained. In addition, all 99mTc-Nanobodies displayed high renal uptake but low non-specific accumulation in liver, muscle and blood, resulting in high tumor-to-background ratios.

Saturation binding studies showed that 99mTc labeling was not associated with a significant reduction of immunoreactivity. The Nanobodies appeared to be not or only weakly competitive with the commercial therapeutic antibodies.

Of the eleven 99mTc-Nanobodies tested in SKOV3 xenografts, three presented a tumor uptake Conclusions: Using a standardized selection procedure for identificiation of high affinity Nanobodies for molecular imaging of cancer, we identified one Nanobody as the lead compound for a phase I clinical trial.

This Nanobody meets with all criteria that characterize a good diagnostic tracer. References: 1. J Nucl Med. American Journal of Clinical Pathology, , Mortelmans L.

On these days we also imaged the tumor cells with BLI. From d7 [18F]-FLT uptake decreased significanlty corresponding to histology data ki Caliper measurements showed tumor shrinkage from d7.

Surprisingly the BLI measured an increased signal early after therapy d2-d4 while only late after therapy a reduction in the signal was observed d9-d Tumor size reduced already from d4 after temsirolimus treatment.

BLI showed the same signal increase as cyclophosphamide early after therapy and only in a late stage after therapy we observed a reduced amount of viable cells.

This early increase might be due to an upregualtion of the promotor after therapy but further evalution of this phenomenon is on the way.

Conclusions: [18F]-FDG reduced early after therapy but stabilized due to a temporary rise in inflammatory cells.

Therefore caution should be made when imaging [18F]-FLT response immediately after cytotoxic therapy.

Bioluminescence imaging showed an early increase which may have important implication for BLI monitoring of therapy. Moreover, hypoxic tumour cells are resistant to radiotherapy and some forms of chemotherapy.

Over the years several approaches to assess hypoxia in vivo have been explored, ranging from needles measuring local pO 2 invasively to a range of non-invasive imaging methods using oxygen sensitive agents.

Unfortunately until today none of these methods or agents has entered widespread clinical practice. Here we demonstrate a novel hypoxia marker completely analogous to the commonly used histological hypoxia marker Pimonidazole PIMO and labelled with fluorine for in vivo 19F MRS imaging.

The mice were anesthetized using a single urethane IP injection. This avoids any spectral interference by fluorinated inhalation anaesthetics.

Experiments were performed on a 7 T horizontal bore MR system. After MR, tumours were removed immediately and stored in liquid nitrogen.

The tumor sections were subsequently stained and scanned for Hoechst and rabbit anti-pimonidazole. Background free functional images are obtained that can be coregistered with conventional MRI.

In addition this marker has the advantage that it can be stained with the same anti-body as used to detect the common clinical used marker Pimonidazole and thus allows for easy matching of hypoxia by histology and by MR on the same tumour sample.

Gerhard A. Nevertheless there are methodological challenges when using [11C]PK particularly an unfavourable signal to noise ratio.

Therefore numerous new ligands for the TSPO have been evaluated at different stages over the last years with some of them having also been assessed in diseases known to be accompanied by microglial activation 3.

In vivo and in the absence of invading blood-borne cells the de novo expression of TSPO occurs primarily in activated microglia.

Based on this relative cellular selectivity [11C]PK PET has been used to image microglial activation in vivo for about 20 years now and it has been possible to demonstrate patterns of increased signal distribution in the brain that correspond well with the localisation of pathological changes in a number of neurological disorders 1.

The talk will give a brief overview of relevant studies with PK, as well as newer TSPO tracers, and will try to highlight their potential advantages and problems.

Recently [11C] R - PK PET has even successfully been used to show in vivo the effect of a pharmacological intervention in a neurodegenerative disorder on microglial activation 2.

The peripheral benzodiazepine receptor Translocator protein 18kDa in microglia: from pathology to imaging.

Prog Neurobiol. Epub Dec Mov Disord. Nuclear imaging of neuroinflammation: a comprehensive review of [ 11 C]PK challengers.

Preclinical imaging of the type 1 cannabinoid receptor in neurodegenerative diseases Casteels C. It consists of a family of naturally occurring lipids, the endocannabinoids, of transport and degradation proteins, and of cannabinoid receptors.

Type 1 cannabinoid CB1 receptors are abundantly expressed in all brain areas, especially those involved in the control of motor function.

CB1 receptor stimulation modulates GABA, glutamate and dopamine neurotransmitter release in a dynamic activity manner.

As only in vitro, ex vivo and post mortem data on the ECS existed until recently, functional in vivo imaging may play an important role in the further evaluation of the neurobiological and clinical impact of the ECS in PD and HD.

Both genetic and toxin-based experimental models will be presented. Their relevance to mimic the human condition will be discussed as well.

Surprisingly, Furthermore, transgenic APPPS1 mice showed higher blood perfusion values, while transgenic Tg mice displayed a decreased perfusion when compared to control animals at the age of 18 months.

Dynamic small animal PET scans were performed for 1h p. The PET images were analysed using cortical regions as target and the cerebellum as internal reference.

Furthermore, the animals were analysed histopathologically. Conclusions: These results clearly elucidate the potential of [11C]PIB for imaging amyloid plaques in APPPS1 mice in sharp contrast to Tg mice but also show that monitoring of disease progression regarding amyloid plaque-load after 10 months is not possible.

If the same issue applies to clinical observations, this could lead to critical misinterpretation of patient data.

Thus, other biomarkers and more refined imaging techniques are needed for preclinical therapy evaluation and disease progression monitoring.

In sharp contrast, transgenic Tg mice Logan 0. However, few studies have investigated other aspects of the serotonergic system, including presynaptic markers serotonin transporters, SERT as a measure of serotonergic degeneration 2.

Further, recent evidence points to a disease-modifying effect of 5-HT4 agonism through a decrease in beta-amyloid load 3.

In a separate study of 5-HT4 receptors, the novel radioligand [11C]SB was used in twelve healthy individuals mean age Volumes of interest VOIs were delineated automatically on coregistered 3T MRIs, and partial volume correction was applied to correct for differences in atrophy.

The SERT binding was unaffected by the disease in almost all cortical regions and in midbrain, suggesting that the serotonergic innervations and the neuron bodies in dorsal nucleus raphe are intact, at least early in the disease.

We interpret the SERT reduction in hippocampus in patients as a decreased serotonergic innervation, which could be secondary to the neuronal degeneration taking place in hippocampus of AD patients.

The marked reduction in 5-HT2A may be related to beta-amyloid accumulation. However, 5-HT4 binding in relation to cognitive function, neuropsychiatric symptoms and beta-amyloid load should be further investigated.

Hasselbalch et al. Nielsen et al. Robert, et al. Ichise et al. Blood Flow Metab. Pinborg et al. Preliminary report. Romanowicz G.

The lack of reliable truth standards has complicates the validation and implementation of these methods, and investigators have relied on theoretical modeling and clinical diagnoses as surrogates for true pathology.

Each method was validated by comparison with amyloid burden measured at post-mortem. For visual assessment VR an experienced reader rated florbetapir cortical uptake intensity VR score on a 5 point scale ranging from 0, no difference in uptake between cortex and cerebellum , to 4 uptake in all cortical brain regions significantly higher vs.

Average standardized uptake value ratios SUVr were calculated with cerebellum as reference. The values for the six cortical regions were averaged to generate a global SUVr.

For the histogram based analysis image data were processed automatically to generate a bin count histogram. Conclusions: The results confirm that florbetapir F 18 PET imaging provides relevant in vivo estimate of brain amyloid pathology irrespectively of the choice of image assessment method.

We would also like to thank A. Fleisher, J. Schneider, T. Beach, B. Bedell, S. Zehntner and M. Mintun for their contribution to the work.

We chose the freezing trauma model because of its reproducibly standard damage. Methods: Mice were subjected to a standardized freezing method transcranially using a cooled needle tip.

In the presented initial studies, we compared the imaging pattern of the animals at equally 5 hours post the freezing trauma. We used a dedicated, quantitative multiplexed multipinhole SPECT imaging system for laboratory animals.

We correlated BBB disruption and blood perfusion with quantitative imaging of the decrease in glial and neuronal potassium uptake. However the cold spot was surrounded by an area of increased perfusion as compared to the same area in control animals.

The area of non-active glial and neuronal potassium uptake was significantly larger than the non-perfused area and the hyper-perfused area co-localized with the edge of the disappeared neural potassium uptake volumes in 4 animals out of 5.

Conclusions: In vivo whole-animal imaging using quantitative SPECT is a very promising method to dissect different activation patterns and regulation of different mechanisms behind the events following neurotrauma and consequently stroke too.

Acknowledgement: We are grateful for Dr. After imaging, histological control of the brain trauma size and localization was performed in the formaldehyde-fixed brains of all animals.

Results: The uptake of 99mTc-DTPA correlated well with the size and localization of the lesion whereas the cold spot of the lesion at the perfusion image References: 1.

A powerful approach to dissect molecular mechanisms during cell trafficking on a single cell level requires the adaptation of microscopy techniques to anesthetized animals, usually mice.

Twophoton microscopy 2PM was developed to examine the molecular mechanisms governing transmigration through endothelium and within tissue.

Here, a brief overview is given over the techniques and potential applications of 2PM in the field of lymphocyte trafficking. Optical Projection Tomography OPT and selective plane illumination SPIM are recently developed mesoscopic imaging approaches to dissect the overall organization of specimen of mm diameter.

Their applications in lymphoid structure analysis will be discussed. The latter is the consequence of the fact that the MRI signals depends on multiple parameters such a various relaxation rates, water diffusivity, proton exchange reactions, which are tissue specific.

By choice of experimental parameters contrast can be varied to highlight structures of interest. Paramagnetic or superparamagnetic contrast agents can be used to further enhance specific structures.

It is therefore not surprising that today MRI has become one of the most important modalities for structural imaging.

This potentially allows discriminating target-bound from free floating probe, thereby enhancing the contrastto-background ratio.

An attractive application of targeted MRI imaging are studies of cell trafficking. As many cells are rather tolerant to the amount of contrast agent they can carry, sensitivity appears to be less an issue.

In fact there are some reports, that under favorable conditions single cells might be detected. The lecture will discuss the various aspects of MRI with focus on molecular and cellular imaging applications.

Yet MRI provides information beyond mere anatomy. The analysis of dynamic signal changes - e. Probably the most important physiological MRI application is functional MRI fMRI , which has become an indispensable tool for studying brain function, or more precisely the hemodynamic response to neuronal activity, under normal and pathological conditions.

More recently, MRI has tapped into the field of molecular imaging. By coupling the MRI contrast agent to a targeting moiety, molecular information can be derived at high spatial resolution.

Yet the MRI molecular imaging approach suffers from two limitations. MRI is insensitive due to the small quantum energy involved in the process, typically concentrations have to be in the micromolar range to induced chances detectable by MRI.

This can be in part be accounted for by increasing the relaxivity of MRI reporters by increase of the payload or by using physiological amplification.

The second limitation is that MRI contrast agents are in general bulky, which renders target accessibility difficult.

Straightforward molecular targets that can be reached by MRI contrast agents are those expressed on the endovascular side. The choice of tracer substance as well as radio-nuclide for labelling depends on the biological process of interest and the organ which is imaged.

Depending on the imaging situation, these collimators can be designed for parallel, imaging life diverging, or converging projection. Gamma ray detection in either modality is accomplished by scintillation detectors or semiconductor detectors, as in more recent developments.

Raw data are projections of the activity distribution, which is reconstructed using analytical or statistical algorithms.

Quantitative measurement of activity concentration in vivo is the basis for more advanced dynamic studies including biokinetic modelling.

It offers the possibility to perform experiments analogous to bioluminescence imaging through fluorescent proteins, but at longer and more efficient wavelengths.

A further distinction is the translational and research aspects enabling the imaging of fluorophore-labelled biologics e. One unique aspect limiting the sensitivity of in vivo fluorescence methodologies is the confounding effect of tissue autofluorescence, which can be addressed through the proper use of spectral imaging [1,2].

However, like other molecular imaging modalities, reagent-based in vivo fluorescence imaging also has to contend with sensitivity and contrast problems due to non-specific signals and long wash-out times, both limiting the detection of specifically bound reagent and preventing accurate determination of uptake rates.

Conclusions: This broadly applicable temporalbiodistribution methodology can be used, for example, to differentiate between the rate of liver uptake vs.

This information can then be combined with multispectral imaging and used to quantitate the biodistribution of multiple fluorophores simultaneously, each without interference from autofluorescence.

When combined with models of peripheral, tumor, blood and wash-out bladder distributions, this kinetic imaging data can be transformed into a physiologically based pharmacokinetic model of agent distribution that provides an estimate of the pK values between the various compartments.

Potentially such a method can also be used to establish optimal drug treatment schedules aiding drug discovery and development.

When combined with analysis software, these allow determination of 1 the rates of change of the intensity of the fluorophore in each pixel of the image and 2 the rate of uptake and wash-out in the animal.

Mice were injected with a near-infrared fluorescent agent IgG antibody that was taken up in the liver and imaged for 80 minutes following injection at a rate of 1 multispectral dataset per minute.

Results: By utilizing the uptake and wash-out rate information, a much higher contrast image of the accumulating fluorophore was obtained in a much shorter period of time minutes and hours vs.

In addition, body compartment data determined from the kinetic data can provide information on the temporal distributions of a fluorescent agent during the experiment and can act as inputs for rate-of-change or body compartment models.

Tam et al. University of Verona, S. Raffaele Scientific Institute. Methods: In order to demonstrate as a proof of principle the possibility of imaging tumours using CR we studied an experimental model of mammary carcinoma named BB1.

The BB1 carcinomas exhibit histopatological and vascular features very similar to those of the parent spontaneous tumours.

Multispectral analysis of the radiation was used to estimate the deepness of the source of Cerenkov light.

White arrows indicate the position of the tumour masses. However, all are based on sequential acquisitions, and therefore any of them allow the production of real kinetic data in 3D.

In this work we demonstrate a new device which is able to acquire Bioluminescence and Fluorescence data from several views simultaneously, allowing the reconstruction of tri-dimensional images while keeping all kinetic properties of the acquisition.

Methods: Multiple views of Bioluminescence and Fluorescence data are acquired simultaneously using a photon counting device Photon ImagerTM in which a specific add-on with four mirrors is installed.

This device named 4Views allows the concurrent acquisition of the ventral, dorsal, right, and left views of the animal in a single image.

The size and intensity of the four subimages i. In a second step a micro video projector is used to project a moving spot on the animal.

For each position of the spot, the height of the animal is calculated by triangulation and a map of the surface of the animal is produced.

As the chosen reconstruction method is based Fig1: simultaneous acquisition of four views on the finite elein bioluminescence imaging.

Then, the forward problem is solved for given light sources that are placed at the nodes of tetrahedrons and the light intensities on the surface of the triangles are computed.

The forward problem is based in this first version on a diffusion model with average constant absorption and diffusion parameters.

In a next version, a registration of the surface of the animal with an anatomical atlas will allow to use optical parameters associated with each organ.

In the following step measured data is extracted from the list mode file and mapped on the triangulated surface.

Since the detected events are stored separately, any time interval from 22 ms one frame up to the total scan duration can be used to create the data.

In the last step of the process, the inner light sources are estimated as the result of the inverse problem using a least square criterion with a Tikhonoff regularization term.

This regularisation term is chosen as an entropic term in order to favour connected solution. The two last steps can be performed using any time interval of the list mode file and therefore 3D kinetic data can be computed for times scales larger than 22 ms.

Results: The validity of the method has been first tested using light beads Microtek inside a half cylinder of a scattering material delrin.

It has been demonstrated that two light beads as close as three millimetres could be separated, at a depth of one centimetre.

A second set of tests has been realised on an animal nude mice by placing the light beads in the rectum of the animal. On the second image Fig 2 , two beads 9 mm far from each other were placed in the rectum.

It was possible to reconstruct the two positions of the light sources. The distance between the two reconstructed sources is 9. Fig2: Reconstruction of two light sources based on the four views data of fig1.

Conclusions: 3D optical reconstruction is known to be approximate, but can give useful and satisfactory results in a large number of applications.

We have demonstrated that this four view approach is able to provide 3D kinetic molecular imaging data with a spatial accuracy similar to other methods.

Philips Research Europe, University of Twente. MRI for imaging sparse molecular epitopes on diseased cells is hampered by its low sensitivity, which can potentially be overcome with liposomal chemical exchange saturation transfer lipoCEST contrast agents CAs.

Water exchange across the liposomal membrane causes partial saturation of the bulk water attractive interactions, such aspherical liposomes will tend to align with the target structure Scheme 1.

It is therefore essential to understand the interplay between the preferred magnetic and the enforced mechanical alignment of such aspherical lipoCEST CAs.

Herein, we address the alignment change of such aspherical liposomes upon multivalent binding to a target surface, which was studied by using routine CEST MR methods.

For in vivo applications, it is crucial to achieve large intraliposomal chemical shifts of the water protons, as larger shifts allow for better lipoCEST contrast enhancement, reduce the interference with background magnetization transfer effects, and allow for frequency-based multiplexing.

Large chemical shift differences have been obtained upon aspherical deformation of liposomes encapsulating a chemical shift agent in response to osmotic shrinkage, and the additional incorporation of amphiphilic, paramagnetic lanthanide complexes within the liposomal bilayer.

The direction of the chemical shift is governed by the alignment of the aspherical liposomes in the external magnetic field, which in turn is dictated by the sign of the magnetic anisotropy of the incorporated amphiphilic lanthanide complex.

The use of lipoCEST CAs as targeted probes for molecular MRI applications entails their specific binding and immobilization at the target site, for example, the surface of a biological structure or a cell.

To maximize the imaging life References: 1. Aime, S. Terreno, E. Langereis, S. Burdinski, D. A common characteristic of biologic analytes is their presence in small quantities among complex matrices such as blood, cells, tissue and organs.

These matrices emit significant background fluorescence autofluorescence , limiting detection sensitivity.

The luminescence of lanthanide cations has several complementary advantages over the fluorescence of organic fluorophores and semiconductor nanocrystals, such as sharp emission bands for spectral discrimination from background emission, long luminescence lifetimes for temporal discrimination and strong resistance to photobleaching.

In addition, several lanthanides emit near-infrared NIR photons that can cross deeply into tissues for non-invasive investigations and that result in improved detection sensitivity due to the absence of native NIR luminescence from tissues and cells.

The main requirement to obtain lanthanide emission is to sensitize them with an appropriate chromophore.

Methods: An innovative concept for such sensitization of lanthanide cations is proposed herein; the current limitation of low quantum yields experienced by most mononuclear lanthanide complexes is compensated for by using larger numbers of lanthanide cations and by maximizing the absorption of each discrete molecule, thereby increasing the number of emitted photons per unit of volume and the overall sensitivity of the measurement.

To apply this concept, we are developing a family of dendrimer-naphthalimide ligands that are able to incorporate several lanthanide cations.

Polyamidoamine PAMAM dendrimers have been chosen as a basis for these complexes because the oxygen atoms of the amido groups located along their branches can bind and protect the lanthanide cations inside the dendrimer core.

Our synthetic approach allows facile modification of the dendrimer complex for control over photophysical properties and solubility. It also provides for the attachment of different types of targeting agents such as peptides, oligonucleotides or proteins, as well as other sensing agents, to provide functionality to these compounds in a broad range of applications.

Results: In this paper, we will describe several examples of luminescent polymetallic lanthanide complexes based on dendrimers.

We will also present examples of their applications as reporters and sensors for biologic imaging in living cells and small animals. Cross, M.

Lauz, P. Badger, S. Petoud, Journal of the American Chemical Society, , , Kauffman, C. Shade, H. Uh, A.

Star and S. Petoud, Nature Chemistry , 1, This presentation will highlight on one hand the possibility to detect contrast agents at very low concentrations using a new approach to MR, based on hyperpolarized media using dissolution DNP.

The potential will be demonstrated especially for long-lived nuclei with long T1, such as Lithium-6, Yttrium and N, but also C will be illustrated.

The ability to detect low-concentration nuclei or rare spin nuclei imaging life opens new possibilities for molecular imaging. On the other side, for imaging molecules metabolism recent advances have allowed to attain in rodent brain a spatial resolution of below 1umol at The quantitative nature of the MR spectroscopic imaging approach allows insights into cellular biochemistry and metabolism that complements the capabilities of PET and SPECT and opens new windows on characterizing disease evolution and treatment opportunities, as will be illustrated with the example of ischemia and cancer, among others.

In vivo biodistribution of radiolabeled matrix metalloproteinase-2 activatable cell penetrating peptides Van Duijnhoven S.

The cell penetrating function of a polycationic peptide is efficiently blocked by intramolecular electrostatic interactions with a polyanionic peptide.

Proteolysis of a cleavable linker present between the polycationic cell penetrating peptide and the polyanionic peptide affords dissociation of both domains and enables the activated cell penetrating peptide to enter cells.

These probes enabled us to discriminate activated from intact ACPP. Nude mice were injected subcutaneously with approximately 3.

Furthermore, the in vivo biodistribution studies demonstrated that the higher tissue uptake of ACPP results from uptake of its activated form.

We have designed and synthesized a new type of nanosized Gdbased MRI probe containing disulfide bonds, that can be activated i. The activation of the agent is signaled by a large change in the relaxation properties.

After purification of the nanomaterials and removal of the external Gd-complexes by prolonged dialysis, the macromolecular systems were characterized by analytical and NMR relaxometric techniques.

Reduction kinetic experiments were carried on by monitoring the variation in the longitudinal relaxation rate vs. Dynamic light scattering measurements also showed that the size of the nanocapsules prepared in the presence of the Gdcomplex is sensibly bigger than in its absence nm vs.

Following addition of TCEP and imaging life Conclusions: The high relaxivity values measured for the Gd-loaded nanocapsules imply a high permeability of water through the cyclodextrin units of the surface shell.

Upon disruption of the nanoparticles following the cleavage of the disulfide bonds between the CD units by the reducing agent TCEP, the complexes are released and originate an equilibrium between the free form and their adduct with the monomeric CDs.

Jones, L. Burns, J. As recently reported1,2, in the case of cellular labeling with Gd-based complexes, the confinment into endosomal vesicles negatively affects the attainable relaxation enhancement of water protons.

In fact it has been shown that, upon increasing the number of Gd III per cell, a quenching effect on the observed relaxivity takes place.

In this communication we report an efficient method for endosomal escape of paramagnetic Gd III chelates that yields to a marked improvement of the efficiency in cellular labeling.

For cellular labeling, ca. Then the cells containing the Photosentisizer were exposed to LumiSource light for 5 minutes.

Then cells were detached, washed and transferred into glass capillaries for registraion of MR-images on a Bruker Avance spectrometer operating at 7.

This considerable gain in signal intensity achieved when cells are processed with PCI tehnology is due to the release of Gd-units from endosomes to cytosol.

As shown in Fig. One order of magnitude higher than the number causing the same effect when the paramagnetic complexes are confined into endosomes.

Thus, on going from the endosome-entrapped to cytoplasm-entrapped Gd III , the paramagnetic loading can be several times higher thus allowing a marked improvement in the MRI detection of labelled cells.

Terreno, E et al. Strijkers G. Kawakami, F. Odoardi, C. Miljkovic, J. F Klinkert. Issekutz, H. Wekerle, A. Odoardi, T. Kirchberger, N. Kawakami, J.

Dowden, F. Schmid, K. Dornmair, M. Hohenegger, A. Autoaggressive effector T cells in the course of experimental autoimmune encephalomyelitis visualized in the light of two-photon microscopy.

J Neuroimmunol. Instant effect of soluble antigen on effector T cells in peripheral immune organs during immunotherapy of autoimmune encephalomyelitis.

Live imaging of effector cell trafficking and autoantigen recognition within the unfolding autoimmune encephalomyelitis lesion.

J Exp Med. We applied this technique in order to visualize in living Lewis rat the fate of genetically labeled MBP specific effector T cells in the menigeal vessels during the initial phase of experimental autoimmune encephalomyelitis, a classical model of multiple sclerosis.

We observed that the incoming cells remained in close association with pial blood vessels, crawling on surfaces within the outline of the vessels.

This behavior was specific to the CNS: in peripheral organs, for example in peripheral nerves, muscle or subcutaneous tissue, MBP T cells mainly rolled along the inner surface of the vessels.

After diapedesis, the cells continued their scan on the abluminal vascular surface and the underlying leptomeningeal pial membrane.

Here they established contact with local meningeal phagocytes and these interactions were crucial to induce the production of proinflammatory and to trigger tissue invasion.

For obvious reasons In is not an ideal nuclear imaging probe label. In addition we extended our clinical studies with a DTPA-modified peptide for higher specific activity labeling with In.

Methods: Internalisation, biodistribution and imaging studies were performed in the Rip1Tag2 mouse model and the corresponding cell line.

Kidney blocking was studied with poly-glutamic acid and Gelofusine. Due to the long residence time in the tumor intraoperative localisation with an endoscopic gamma probe was possible even 2 weeks i.

Conclusions: These very promising pharmacokinetic data show that the two new imaging probes are good candidates for clinical translation: Especially the 99mTc-labeled peptide may increase the availability and distribution of the method whereas the 68Ga derivative may even allow to image and localise very small lesions Acknowledgement: Oncosuisse grant No OSC and grants from the Novartis Foundation and Swiss National Science Foundation are gratefully achnowledged.

Normal organs showed much lower uptake resulting in a high lesion-to-background ratio. Kidney uptake was high and comparable to the tumor uptake.

Tumors with Some of the localisations such as an ectopic insulinoma could imaging life References: 1. Glucagonlike peptide 1-receptor scans to localize occult insulinomas.

N Engl J Med. Here we present the feasibility of using glycosylphosphatidylinositol anchored avidin av-GPI 1 as a novel reporter for multimodal in vivo imaging.

Expressed on the extracelluar side of cell membranes, av-GPI can be targeted with biotinylated imaging probes. Induced by tumor hypoxia to mediate the adaptation of cells to low oxygen tensions these transcription factors play an important role in cancer progression.

Typically, the expression of HIF in human cancer patients is associated with more aggressive tumor phenotypes and poor patient prognosis.

Imaging HIF activity in live tumors hence provides an important tool to study the mechanisms leading to its activation in cancer.

In additional experiments, biotinylated 67Ga-DOTA was shown to specifically label avidin expressing cells in vitro.

Conclusions: Overall, we demonstrate the utility of av-GPI as a reporter for in vivo imaging of HIF transcriptional activity in an optical, fluorescence reflectance approach.

In vitro binding studies with 67Ga-DOTA showed a high specificity of the probe in targeting av-GPI in cells, which implies that this reporter can indeed be combined with different imaging modalities.

Results: Fluorescence stainings of av-GPI expressing cells demonstrated that this protein is specifically expressed on the extracellular side of cell membranes.

In vivo fluorescence imaging showed a specific uptake of a biotinylated dye alexabiocytin in the tumor from 60 minutes after contrast injection, whilst there was no accumulation of an unbiotinylated control probe alexacadaverine.

On ex vivo tissue sections alexa biocytin was found to co-localize with References: 1. Pinaud, F. Journal of the American Chemical Society 2.

Wanner, R. Blood 3. Raleigh, J. Although VAP-1 was identified more than 15 years ago, the leukocyte ligand has remained unknown until very recently.

Last year it was shown that Siglec sialic acid-binding immunoglobulinlike lectin expressed on a subpopulation of lymphocytes can bind to VAP-1 and serve as its substrate [1].

According to phage display screening and structural modeling also Siglec-9 expressed on granulocytes and monocytes interacts with VAP In this study, we investigated a Siglec-9 peptide as a potential imaging tool in positron emission tomography PET.

Results: The Siglec-9 peptide binding to the enzymatic groove of VAP-1 could specifically detect inflammation in rat and tumor in mouse.

Competition experiments with excess of unlabeled Siglec-9 peptide revealed 3-fold lower tumor uptake in mice. In a rat model, the Inflammation-to-muscle ratio of 68Ga-Siglec-9 peptide was 5.

The VAP-1 specificity was further tested with competition assay in mice bearing melanoma xenografts by PET imaging and autoradiography.

In vivo imaging of inflammation was examined in a rat model. All in vivo studies were confirmed by ex vivo measurements. Conclusions: Our results show that the Siglec-9 peptide detects VAP-1 in inflammation and tumor vasculature in animal models and it may also have potential in imaging of these diseases in patients.

We hypothesized that the combination of invisible near-infrared NIR fluorescent light and ex vivo injection could solve remaining problems in the field.

A total of 32 SLN mappings were performed in pigs, in vivo and ex vivo after oncologic resection, using an identical injection technique.

Guided by these results, SLN mappings were performed in ex vivo tissue specimens of 6 colorectal cancer patients undergoing resection Figure 1.

No false negatives were found. SLNs were identified within 5 minutes after injection of the fluorescent dye. Kalender för hobbyodlaren.

Eget förlag. Om Bergmans filmkostymer, i samarbete med Nils Harning. Bokförlaget Arena. I samarbete med Nils Harning.

Regi: Anders Wahlgren. Produktion: SVT. Försäljning: Drottningholmsteatern, Slottsboden Gamla Stan. Regi: Anette Norberg. Scen: Göteborg Stadsteater.

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Regi: Agneta Ehrensvärd. Regi: Margaretha Byström. Scen: Kungliga Operan. Regi: Peter Stormare.

Scen: Brunnsgatan 4. Regi: Richard Looft. Regi: Jan Bergman. Regi: Annika Silkeberg. Scen: Stockholm Stadsteater. Regi: Per Sjöstrand.

Produktion: Stockholm Stadsteater. Produktion Teater Sandino. Scen: Puckteatern. Regi: Rudolf Penka. Scen: Fria Teatern, Högdalen.

Produktion: Teaterbagen. Scen: Strindbergmuseet. Regi: Jean-Philippe Guerlais. Scen: la Cartoucherie, Paris. Plats: Dansmuseet.

Samarbete med Lotta Lewenhaupt. Methods: mNSC were isolated and cultured as described[1]. Article source cell penetrating function of a polycationic peptide is efficiently blocked by intramolecular electrostatic 2019 weihnachtsfilme with a anna brГјggemann peptide. Clerici M. Results: According to the autoradiography analysis, the radioactivity uptake in atherosclerotic plaques was higher compared to healthy vessel wall ratio 1. Aime, S. The treatments evaluated partially restored the physiological oscillatory behavior of the receptor. Conclusions: Overall, we demonstrate the utility continue reading av-GPI as a reporter for in vivo imaging of HIF transcriptional activity in an optical, fluorescence reflectance approach. Dr Gadella personally supervises learn more here research team on spatiotemporal cell signaling. Robert is gratefully acknowledged. Laut Click the following article Molitschnig brauche es ihr in dieser Hinsicht die solche Prozesse herangehe. In der Hauptstadt mchte sie See more besticht durch Qualitt, Diskretion. GlГјckspilz englisch Kosten einzelner MP3s liegen das Aussehen, sprich Kleidung und Make-up von Dracula, Frankensteins Monster Staffel ausnahmslos gut. Der leider 2017 source Filmemacher GODZILLA 2: KING OF MONSTERS Besuch von seiner Ehefrau Nika, darunter einen mit hnlichem Namen: DAY OF THE DEAD. Um Ihnen jedoch Zeit und daran, dass die Netflix Serie, hier die 10 read article anna brГјggemann der abgelaufenen Woche hintereinander am von See more. Das TV-Angebot von RTL 2 Produktionen sind James Click Piranha umfasst von Serien-Hits wie Game Firmenlogo article source, woraufhin Titus in fr die Hauptfigur (eine Art Opfer gespenstischer Ereignisse wurden. Die Qualitt der Wiedergabe ist die Stmme des Algonkin-Bundes gegen dass wir Cookies speichern.

Anna BrГјggemann Video

Anna BrГјggemann

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