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Imaging Biomarkers or Biomarker Imaging?

Markus Mitterhauser, Wolfgang Wadsak
2014 Pharmaceuticals  
Since biomarker imaging is traditionally understood as imaging of molecular probes, we highly recommend to avoid any confusion with the previously defined term "imaging biomarkers" and, therefore, only use "molecular probe imaging (MPI)" in that context. Molecular probes (MPs) comprise all kinds of molecules administered to an organism which inherently carry a signalling moiety. This review highlights the basic concepts and differences of molecular probe imaging using specific biomarkers. In
more » ... ticular, PET radiopharmaceuticals are discussed in more detail. Specific radiochemical and radiopharmacological aspects as well as some legal issues are presented.
doi:10.3390/ph7070765 pmid:24967536 pmcid:PMC4113731 fatcat:mgyp4d6z7ja77kyf5t2onwcv3u

The Potential Role of the MCHR1 in Diagnostic Imaging: Facts and Trends [chapter]

Cécile Philippe, Markus Mitterhauser
2017 Melanin  
Cécile Philippe 1* and Markus Mitterhauser 1, 2 *Address all correspondence to: cecile.philippe@meduniwien.ac.at 1 Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine  ... 
doi:10.5772/67185 fatcat:j3b3ewjrvvhqfmqj2zktgls7lq

Experimental Nuclear Medicine Meets Tumor Biology

Theresa Balber, Loan Tran, Katarína Benčurová, Julia Raitanen, Gerda Egger, Markus Mitterhauser
2022 Pharmaceuticals  
Personalized treatment of cancer patients demands specific and validated biomarkers for tumor diagnosis and therapy. The development and validation of such require translational preclinical models that recapitulate human diseases as accurately as possible. Moreover, there is a need for convergence of different (pre)clinical disciplines that openly share their knowledge and methodologies. This review sheds light on the differential perception of biomarkers and gives an overview of currently used
more » ... models in tracer development and approaches for biomarker discovery.
doi:10.3390/ph15020227 pmid:35215337 pmcid:PMC8878163 fatcat:xjh7itwykzdphduucihakosqou

A PET microdosing study with the P-glycoprotein inhibitor tariquidar

Martin Bauer, Markus Zeitlinger, Cécile Philippe, Johann Stanek, Wolfgang Wadsak, Markus Mitterhauser, Georgios Karanikas, Markus Müller, Oliver Langer
2012 BMC Pharmacology and Toxicology  
The adenosine triphosphate-binding cassette transporters P-glycoprotein (Pgp) and breast cancer resistance protein (BCRP) restrict absorption and body distribution and promote excretion of several clinically used drugs. Tariquidar (XR9576) is a potent third-generation dual Pgp and BCRP inhibitor, which is currently tested in clinical trials to overcome chemoresistance of tumors and to enhance brain distribution of Pgp/BCRP substrate drugs. We performed a positron emission tomography (PET)
more » ... osing study with carbon-11-labelled tariquidar ([ 11 C]tariquidar) which aimed at assessing the brain distribution of [ 11 C]tariquidar in healthy volunteers. Methods Six healthy subjects received an i.v. bolus injection of approximately 400 MBq of [ 11 C]tariquidar containing less than 30 µg of unlabelled tariquidar. Then, dynamic brain PET scans and arterial blood sampling were performed. Radiolabelled metabolites of [ 11 C]tariquidar in plasma were measured with a solid-phase extraction/HPLC assay. Brain activity uptake was expressed as the ratio of the area under the whole brain grey matter time-activity curve to the area under the plasma time-activity curve from time 0 to 60 min (AUC 0-60 brain /AUC 0-60 plasma ). Results Brain activity uptake was low after injection of [ 11 C]tariquidar with a mean AUC 0-60 brain /AUC 0-60 plasma of 0.14 ± 0.03. At 60 min after radiotracer injection, 78 ± 12% of total radioactivity in plasma was in the form of unchanged parent radiotracer. Less than 1% of the total injected dose excreted in urine over 90 min.
doi:10.1186/2050-6511-13-s1-a17 pmcid:PMC3506280 fatcat:743aro6z4fcoxcumax24gkdyta

An in vitro model for the comparative evaluation of bone seeking pharmaceuticals

Markus Mitterhauser
2008 ALTEX: Alternatives to Animal Experimentation  
Radioactively labelled polyphosphonate (content of ligand: 0.3 µmol, based on commercially available radiolabelling kits) Mitterhauser et al., 2005; Toegel et al., 2006a; Mitterhauser et al., 2007) or  ...  Comparing Table 1 and both matrices (Mitterhauser et al., 2005; Toegel et al., 2006a; Toegel et al., 2007) .  ... 
doi:10.14573/altex.2008.1.51 fatcat:czbbxbee6ja6tj23f7hmvp6xgq

High-Dose Testosterone Treatment Increases Serotonin Transporter Binding in Transgender People

Georg S. Kranz, Wolfgang Wadsak, Ulrike Kaufmann, Markus Savli, Pia Baldinger, Gregor Gryglewski, Daniela Haeusler, Marie Spies, Markus Mitterhauser, Siegfried Kasper, Rupert Lanzenberger
2015 Biological Psychiatry  
BACKGROUND: Women are two times more likely to be diagnosed with depression than men. Sex hormones modulating serotonergic transmission are proposed to partly underlie these epidemiologic findings. Here, we used the cross-sex steroid hormone treatment of transsexuals seeking sex reassignment as a model to investigate acute and chronic effects of testosterone and estradiol on serotonin reuptake transporter (SERT) binding in female-to-male and male-to-female transsexuals. METHODS: Thirty-three
more » ... nssexuals underwent [ 11 C]DASB positron emission tomography before start of treatment, a subset of which underwent a second scan 4 weeks and a third scan 4 months after treatment start. SERT nondisplaceable binding potential was quantified in 12 regions of interest. Treatment effects were analyzed using linear mixed models. Changes of hormone plasma levels were correlated with changes in regional SERT nondisplaceable binding potential. RESULTS: One and 4 months of androgen treatment in female-to-male transsexuals increased SERT binding in amygdala, caudate, putamen, and median raphe nucleus. SERT binding increases correlated with treatment-induced increases in testosterone levels, suggesting that testosterone increases SERT expression on the cell surface. Conversely, 4 months of antiandrogen and estrogen treatment in male-to-female transsexuals led to decreases in SERT binding in insula, anterior, and mid-cingulate cortex. Increases in estradiol levels correlated negatively with decreases in regional SERT binding , indicating a protective effect of estradiol against SERT loss. CONCLUSIONS: Given the central role of the SERT in the treatment of depression and anxiety disorders, these findings may lead to new treatment modalities and expand our understanding of the mechanism of action of antidepressant treatment properties.
doi:10.1016/j.biopsych.2014.09.010 pmid:25497691 pmcid:PMC4585531 fatcat:xmtun33g5re5bbwofnjlscghzy

[18F]FE@SNAP—a specific PET tracer for melanin-concentrating hormone receptor 1 imaging?

Cécile Philippe, Daniela Haeusler, Thomas Scherer, Clemens Fürnsinn, Markus Zeilinger, Wolfgang Wadsak, Karem Shanab, Helmut Spreitzer, Marcus Hacker, Markus Mitterhauser
2016 EJNMMI Research  
The melanin-concentrating hormone receptor 1 (MCHR1), which is highly expressed in the lateral hypothalamus, plays a key role in energy homeostasis, obesity and other endocrine diseases. Hence, there is a major interest in in vivo imaging of this receptor. A PET tracer would allow non-invasive in vivo visualization and quantification of the MCHR1. The aim of the study was the ex vivo evaluation of the MCHR1 ligand [ 18 F]FE@SNAP as a potential PET tracer for the MCHR1. Methods: [ 18 F]FE@SNAP
more » ... s injected directly into the jugular vein of awake naïve rats for ex vivo brain autoradiography, biodistribution and additional blood metabolite analysis. Blocking experiments were conducted using the unlabeled MCHR1 ligand SNAP-7941. Results: A high uptake of [ 18 F]FE@SNAP was observed in the lateral hypothalamus and the ventricular system. Both regions were significantly blocked by SNAP-7941. Biodistribution evinced the highest uptake in the kidneys, adrenals, lung and duodenum. Specific blocking with SNAP-7941 led to a significant tracer reduction in the heart and adrenals. In plasma samples, 47.73 ± 6.1 % of a hydrophilic radioactive metabolite was found 45 min after tracer injection. Conclusions: Since [ 18 F]FE@SNAP uptake was significantly blocked in the lateral hypothalamus, there is strong evidence that [ 18 F]FE@SNAP is a highly suitable agent for specific MCHR1 imaging in the central nervous system. Additionally, this finding is supported by the specific blocking in the ventricular system, where the MCHR1 is expressed in the ependymal cells. These findings suggest that [ 18 F]FE@SNAP could serve as a useful imaging and therapy monitoring tool for MCHR1-related pathologies.
doi:10.1186/s13550-016-0186-7 pmid:27033361 pmcid:PMC4816952 fatcat:jrslr6fuqba4zc4bywavtfeb3q

Development and evaluation of a rapid analysis for HEPES determination in 68Ga-radiotracers

Sarah Pfaff, Tina Nehring, Verena Pichler, Jens Cardinale, Markus Mitterhauser, Marcus Hacker, Wolfgang Wadsak
2018 EJNMMI Research  
HEPES is a favorable buffer for 68Ga-complexations in radiochemical laboratories. The drawback of this buffer is its prescribed limit of 200 μg per recommended application volume in the final formulation. Currently, a TLC test according to the European Pharmacopoeia (Ph. Eur.) has to be performed for quantification, but this analysis suffers from low reliability and reproducibility and is based on a subjective, semi-quantitative visual evaluation. In this study, the TLC method according to the
more » ... h. Eur. and two literature-known HPLC assays for HEPES quantification were evaluated. Additionally, the development of an improved TLC method was performed. The assay according to Antunes et al. provided a reasonable quantification of HEPES using HPLC. Additionally, a reliable and conclusive TLC method was developed, which facilitates quantitative analysis by means of a pixel-based evaluation. A comparison of those two methods with the Ph. Eur. TLC assay pinpoints the superiority of the HPLC as well as the new TLC assay. Furthermore, evaluation of HEPES contents using both TLC assays by 28 subjects supported the conclusion that the newly developed TLC method is clearly favorable. The TLC method according to the Ph. Eur. provides unsatisfactory results in terms of conclusiveness and reproducibility. In contrast, a reported HPLC assay showed valid results, with the drawback of high technical effort. An optimized alternative is provided by the improved TLC method described in this work that results in reliable outcomes and additionally offers quantitative analysis.
doi:10.1186/s13550-018-0449-6 pmid:30353250 pmcid:PMC6199202 fatcat:yklra5k7tnhlvohtccyn7mdgwy

Prospective non-invasive evaluation of CXCR4 expression for the diagnosis of MALT lymphoma using [68Ga]Ga-Pentixafor-PET/MRI

Alexander R. Haug, Asha Leisser, Wolfgang Wadsak, Markus Mitterhauser, Sarah Pfaff, S. Kropf, Hans-Juergen Wester, Marcus Hacker, Markus Hartenbach, Barbara Kiesewetter-Wiederkehr, Markus Raderer, Marius E. Mayerhoefer
2019 Theranostics  
MALT lymphomas express the chemokine receptor CXCR4 on a regular basis, and [68Ga]Ga-Pentixafor-PET has been shown to quantify CXCR4 expression non-invasively. We, therefore, aimed to evaluate [68Ga]Ga-Pentixafor-PET/MRI for the non-invasive assessment of MALT lymphomas.
doi:10.7150/thno.31032 pmid:31281504 pmcid:PMC6587159 fatcat:jyai56zalvgmhnxieqeebbdyiu

[11C]acetate PET as a tool for diagnosis of liver steatosis

Marzieh Nejabat, Asha Leisser, Georgios Karanikas, Wolfgang Wadsak, Markus Mitterhauser, Marius Mayerhöfer, Christian Kienbacher, Michael Trauner, Marcus Hacker, Alexander R. Haug
2018 Abdominal Radiology  
Purpose: To investigate [ 11 C]acetate PET-surrogate parameter of fatty acid synthase activity-as suitable tool for diagnosis and monitoring of liver steatosis Methods: In this retrospective study, data were obtained from 83 prostatic carcinoma patients from 1/2008 to 1/2014. Mean HU was calculated from unenhanced CT of all patients from liver with liver HU less than 40 as threshold for liver steatosis. SUV max of the liver and of the blood pool in thoracic aorta (as background for calculation
more » ... f a liver/background ratio [SUV l/b ]) was measured. t test was used with a P < 0.05 considered as statistically significant difference and ROC analysis was used for calculating specificity and sensitivity. Results: 19/83 patients (20%) had diagnosis of hepatic steatosis according to CT. Uptake of [ 11 C]acetate was significantly higher in patients with hepatic steatosis as compared to control group (SUV max 7.96 ± 2.0 vs. 5.48 ± 2.3 [P < 0.001]). There was also a significant correlation between both SUV max (r = -0.52, P < 0.001) and SUV l/b (r = -0.59, P < 0.001) with the density (HU) of the liver. In ROC analysis for detection of liver steatosis SUV max (threshold: 5.86) had a sensitivity of 94% and specificity of 69% with an AUC of 0.81. Increasing body mass index is correlated with the severity of steatosis. Conclusion: We showed for the first time that hepatic steatosis associates with increased [ 11 C]acetate uptake. Also, severity of steatosis correlates with [ 11 C]acetate uptake. [ 11 C]acetate uptake PET seems promising for the assessment of liver steatosis.
doi:10.1007/s00261-018-1558-4 pmid:29644441 fatcat:m3ezpsl44bdf3oc7chshoyvpsa

EGFR is required for FOS‐dependent bone tumor development via RSK2/CREB signaling

Markus Linder, Elisabeth Glitzner, Sriram Srivatsa, Latifa Bakiri, Kazuhiko Matsuoka, Parastoo Shahrouzi, Monika Dumanic, Philipp Novoszel, Thomas Mohr, Oliver Langer, Thomas Wanek, Markus Mitterhauser (+2 others)
2018 EMBO Molecular Medicine  
shown by decreased PCNA and elevated cleaved caspase-3 IHC staining 2 of 15 EMBO Molecular Medicine 10: e9408 | 2018 ª 2018 The Authors EMBO Molecular Medicine EGFR promotes osteosarcoma development Markus  ... 
doi:10.15252/emmm.201809408 fatcat:vntanulxmvcqzd6gagzk3rep7u

Attenuation Correction Approaches for Serotonin Transporter Quantification With PET/MRI

Lucas Rischka, Gregor Gryglewski, Neydher Berroterán-Infante, Ivo Rausch, Gregory Miles James, Manfred Klöbl, Helen Sigurdardottir, Markus Hartenbach, Andreas Hahn, Wolfgang Wadsak, Markus Mitterhauser, Thomas Beyer (+4 others)
2019 Frontiers in Physiology  
Copyright © 2019 Rischka, Gryglewski, Berroterán-Infante, Rausch, James, Klöbl, Sigurdardottir, Hartenbach, Hahn, Wadsak, Mitterhauser, Beyer, Kasper, Prayer, Hacker and Lanzenberger.  ... 
doi:10.3389/fphys.2019.01422 pmid:31824335 pmcid:PMC6883225 fatcat:qdtangoubvbffeg3m7yymsk5n4

DHEAS and cortisol correlate with Hypothalamic Serotonin-1A Receptors

Ulrike Moser, Wolfgang Wadsak, Patrycja Stein, Christoph Spindelegger, Markus Mitterhauser, Alexander Holik, Christian Bieglmayer, Kurt Kletter, Siegfried Kasper, Rupert Lanzenberger
2008 Annals of General Psychiatry  
Serotonin modulates the activity of the hypothalamicpituitary-adrenal (HPA) axis, to a big part through the serotonin-1A receptor (5-HT1A) [1]. In return, hormones of the HPA axis, namely dehydroepiandrosterone sulfate (DHEAS) [2] and cortisol have regulatory effects on the serotonergic neurotransmission. Materials and methods Eighteen healthy female subjects participated in this PET study. The selective 5-HT1A receptor antagonist [carbonyl-11C]WAY-100635 was used as radioligand. The
more » ... s as an essential part of the HPA axis and eight control regions of interest and the cerebellum as reference region were defined a priori and delineated on coregistered MR images. DHEAS and cortisol plasma levels were ascertained by morning blood collections on the PET day. The 5-HT1A receptor binding potentials of the target brain regions were correlated with DHEAS, cortisol plasma levels and the ratio of DHEAS / cortisol. Results We found highly significant correlations between the hypothalamic 5-HT1A receptor binding and DHEAS (p=.003) and the ratio of DHEAS / cortisol (p<.0001), but not with cortisol and not in other brain regions. Conclusions The 5-HT1A receptor may influence the DHEAS plasma level by modulating CRH and ACTH release as reported for cortisol before [1] . Vice versa, the interaction of cortisol and DHEAS may exert a regulatory effect on the 5-HT1A receptor distribution in the hypothalamus as a feedback loop. As disturbances of the HPA axis [3] as well as changes of the 5-HT1A receptor distribution [4] have been reported frequently in affective disorders, future studies should aim their focus on these interactions.
doi:10.1186/1744-859x-7-s1-s220 fatcat:lflvilh32nfehilitwkqe62pai

Normative database of the serotonergic system in healthy subjects using multi-tracer PET

Markus Savli, Andreas Bauer, Markus Mitterhauser, Yu-Shin Ding, Andreas Hahn, Tina Kroll, Alexander Neumeister, Daniela Haeusler, Johanna Ungersboeck, Shannan Henry, Sanaz Attaripour Isfahani, Frank Rattay (+3 others)
2012 NeuroImage  
Database 5-HT1A 5-HT2A 5-HT1B 5-HTT The highly diverse serotonergic system with at least 16 different receptor subtypes is implicated in the pathophysiology of most neuropsychiatric disorders including affective and anxiety disorders, obsessive compulsive disorder, post-traumatic stress disorder, eating disorders, sleep disturbance, attention deficit/ hyperactivity disorder, drug addiction, suicidal behavior, schizophrenia, Alzheimer, etc. Alterations of the interplay between various pre-and
more » ... tsynaptic receptor subtypes might be involved in the pathogenesis of these disorders. However, there is a lack of comprehensive in vivo values using standardized procedures. In the current PET study we quantified 3 receptor subtypes, including the major inhibitory (5-HT 1A and 5-HT 1B ) and excitatory (5-HT 2A ) receptors, and the transporter (5-HTT) in the brain of healthy human subjects to provide a database of standard values. PET scans were performed on 95 healthy subjects (age=28.0±6.9 years; 59% males) using the selective radioligands [carbonyl-11 C]WAY-100635, [ 11 C]P943, [ 18 F]altanserin and [ 11 C]DASB, respectively. A standard template in MNI stereotactic space served for region of interest delineation. This template follows two anatomical parcellation schemes: 1) Brodmann areas including 41 regions and 2) AAL (automated anatomical labeling) including 52 regions. Standard values (mean, SD, and range) for each receptor and region are presented. Mean cortical and subcortical binding potential (BP) values were in good agreement with previously published human in vivo and post-mortem data. By means of linear equations, PET binding potentials were translated to post-mortem binding (provided in pmol/g), yielding 5.89 pmol/g (5-HT 1A ), 23.5 pmol/g (5-HT 1B ), 31.44 pmol/g (5-HT 2A ), and 11.33 pmol/g (5-HTT) being equivalent to the BP of 1, respectively. Furthermore, we computed individual voxel-wise maps with BP values and generated average tracer-specific whole-brain binding maps. This knowledge might improve our interpretation of the alterations taking place in the serotonergic system during neuropsychiatric disorders.
doi:10.1016/j.neuroimage.2012.07.001 pmid:22789740 fatcat:b2pwlthdjbeinjvhuosmhyhzu4

1-(3-Amino-1-phenylpropyl)-3-(2-fluorophenyl)-1,3-dihydro-2H-benzimidazol-2-one

Catharina Neudorfer, Nadine Eberherr, Karem Shanab, Wolfgang Holzer, Christina Rami-Mark, Markus Mitterhauser, Wolfgang Wadsak, Helmut Spreitzer
2015 Molbank  
Starting from 1-(2-fluorophenyl)-1,3-dihydro-2H-benzimidazol-2-one (1) and (1-bromo-3-chloropropyl)benzene (2), the target compound 3, which represents a precursor for future radiolabeling, is prepared in a three-step synthesis.
doi:10.3390/m867 fatcat:dfta3birczbiree45oezb4haee
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