Article
Chemistry, Multidisciplinary
Irene Hernandez-Lozano, Severin Mairinger, Thomas Filip, Michael Sauberer, Thomas Wanek, Johann Stanek, Johannes A. Sake, Thomas Pekar, Carsten Ehrhardt, Oliver Langer
Summary: The study demonstrates that P-glycoprotein can affect the pulmonary disposition of inhaled drugs, with decreased P-gp activity potentially leading to lower lung exposure and decreased therapeutic efficacy. PET imaging with intratracheally aerosolized radiotracers shows promise for assessing the impact of membrane transporters on pulmonary drug delivery in both rodents and potentially in humans.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Endocrinology & Metabolism
Severin Mairinger, Sarah Leterrier, Thomas Filip, Mathilde Loebsch, Jens Pahnke, Irene Hernandez-Lozano, Johann Stanek, Nicolas Tournier, Markus Zeitlinger, Marcus Hacker, Oliver Langer, Thomas Wanek
Summary: This study investigated the sensitivity of [C-11]metoclopramide in measuring decreased cerebral P-gp function using mouse models. The results showed that [C-11]metoclopramide could effectively differentiate mice with varying levels of cerebral P-gp expression without the need for a P-gp inhibitor.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Yong Du, Jennifer M. Coughlin, Mary Katherine Brosnan, Allen Chen, Laura K. Shinehouse, Rehab Abdallah, Martin A. Lodge, William B. Mathews, Chen Liu, Yunkou Wu, Il Minn, Paige Finley, Andrew W. Hall, Wojciech G. Lesniak, Robert F. Dannals, Andrew G. Horti, Martin G. Pomper
Summary: In this study, the safety and pharmacokinetic behavior of [C-11]MDTC in healthy human brain were evaluated using positron emission tomography (PET). The study found low expression of the cannabinoid receptor type 2 (CB2R) in the brain. Test-retest reliability of the receptor-binding outcomes showed a mean absolute variability of 9.91%. The results demonstrate the potential of [C-11]MDTC PET in assessing CB2R expression in the human brain.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Martin Bauer, Sandra Barna, Matthias Blaickner, Konstantin Prosenz, Karsten Bamminger, Verena Pichler, Nicolas Tournier, Marcus Hacker, Markus Zeitlinger, Georgios Karanikas, Oliver Langer
Summary: The new PET tracer [C-11]metoclopramide showed predominant uptake in the liver with renal and biliary excretion of radioactivity. The mean effective dose was comparable to other C-11-labeled PET tracers, and the urinary bladder and liver received the highest radiation doses. Overall, [C-11]metoclopramide was found to be safe and well tolerated in healthy adults.
MOLECULAR IMAGING AND BIOLOGY
(2021)
Article
Radiology, Nuclear Medicine & Medical Imaging
Nakul Ravi Raval, Clara Aabye Madsen, Vladimir Shalgunov, Arafat Nasser, Umberto Maria Battisti, Emily Eufaula Beaman, Morten Juhl, Louise Moller Jorgensen, Matthias Manfred Herth, Hanne Demant Hansen, Pontus Plav, Gitte Moos Knudsen
Summary: This study tested the effectiveness of a PET radiotracer (d3)-[11C]MODAG-001 in pig brains. Results showed increased binding of the radiotracer after injection of alpha-synuclein aggregates and Alzheimer's disease brain homogenate. Despite limited specificity, this radiotracer shows promise for future radiotracer development.
NUCLEAR MEDICINE AND BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Severin Mairinger, Irene Hern, Thomas Filip, Michael Sauberer, Mathilde Lobsch, Johann Stanek, Thomas Wanek, Johannes A. Sake, Thomas Pekar, Carsten Ehrhardt, Oliver Langer
Summary: This study used positron emission tomography (PET) imaging to investigate the influence of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) on the pulmonary distribution of inhaled drugs. The results showed functional activity of P-gp and BCRP in the lungs and suggested that these transporters play a role in limiting the uptake of drugs in the lungs, similar to the blood-brain barrier. The study highlights the importance of pulmonary efflux transporters in the efficacy and safety of inhaled drugs.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Endocrinology & Metabolism
Kelly Smart, Heather Liu, David Matuskey, Ming-Kai Chen, Kristen Torres, Nabeel Nabulsi, David Labaree, Jim Ropchan, Ansel T. Hillmer, Yiyun Huang, Richard E. Carson
Summary: The study suggests that the tissue influx and binding potential of the positron emission tomography radioligand [C-11]UCB-J are influenced by neural activation, while the volume of distribution remains stable. K(1) significantly increased during stimulation in the primary visual cortex, correlating with fMRI BOLD response.
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
(2021)
Article
Chemistry, Multidisciplinary
Melodie Ferrat, Kenneth Dahl, Magnus Schou
Summary: The preparation of electrophilic C-11-labelled aroyl dimethylaminopyridinium salts through carbonylative cross-coupling provides valuable intermediates for synthesizing primary [C-11]benzamides. This method yields benzamide model compounds, including PARP inhibitors, with moderate to excellent radiochemical yields, paving the way for potential application in PET tracer synthesis.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Inorganic & Nuclear
Daniel F. Earley, Jose Esteban Flores, Amaury Guillou, Jason P. Holland
Summary: In recent years, copper-64 and copper-67 have been considered as a useful theranostic pair in nuclear medicine. This study successfully demonstrates the viability of photochemically induced conjugation methods for the development of copper-based radiotracers for potential applications in diagnostic PET imaging and targeted radionuclide therapy.
DALTON TRANSACTIONS
(2022)
Article
Chemistry, Medicinal
Emily Murrell, Junchao Tong, David Smil, Taira Kiyota, Ahmed M. Aman, Methvin B. Isaac, Iain D. G. Watson, Neil Vasdev
Summary: Through the development of C-11-labeled radiotracers, a potential brain-penetrant ALK2 inhibitor has been successfully demonstrated to evenly permeate into the pons, showing high initial brain uptake in healthy Sprague-Dawley rats.
ACS MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Chemistry, Multidisciplinary
Tatsuya Kikuchi, Masanao Ogawa, Toshimitsu Okamura, Antony D. Gee, Ming-Rong Zhang
Summary: This study reports a simple and efficient method for the production of [C-11]HCN that can be easily implemented in C-11 production facilities, eliminating the need for a dedicated infrastructure.
Article
Chemistry, Organic
Jonas Rydfjord, Silav Al-Bazaz, Sara Roslin
Summary: Positron emission tomography (PET) is an important imaging technique with various clinical applications. This study presents a method for labeling acyl amidines and 1,2,4-oxadiazoles with carbon-11 using palladium-mediated carbonylation synthesis. The method demonstrated good radiochemical yields and high molar activity, indicating its utility for incorporating carbon-11 into pharmacologically relevant structural motifs.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Medicine, Research & Experimental
Kavya Prasad, Erik F. J. de Vries, Jurgen W. A. Sijbesma, Lara Garcia-Varela, Daniel A. Vazquez-Matias, Rodrigo Moraga-Amaro, Antoon T. M. Willemsen, Rudi A. J. O. Dierckx, Aren van Waarde
Summary: This study investigates the regulation of A(2A) receptors on D-2 receptor binding using positron emission tomography (PET) technique. It shows that the A(2A) agonist CGS21680 can reduce the availability of D2 receptors in the striatum.
MOLECULAR PHARMACEUTICS
(2022)
Article
Chemistry, Multidisciplinary
Dingyao Gao, Yinxing Miao, Siqin Ye, Chunmei Lu, Gaochao Lv, Ke Li, Chunjing Yu, Jianguo Lin, Ling Qiu
Summary: GGT is a key biomarker for cancer diagnosis due to its high expression in malignant tumors. A novel PET imaging probe, [F-18]GCPA(2), has been designed for targeted monitoring of GGT expression in living subjects, showing potential for clinical applications.
Review
Biochemistry & Molecular Biology
Michael R. Kilbourn
Summary: The application of positron emission tomography (PET) imaging to study brain biochemistry, especially dopamine neurotransmission, has significantly grown over the past 40 years. PET imaging of dopaminergic functions in the central nervous system is routinely used for research in neurology, psychiatry, drug abuse and addiction, as well as drug development. The key advancement in PET imaging is the development of unique radiotracers labeled with positron-emitting radionuclides like carbon-11 and fluorine-18, which have greatly contributed to the progress in this field.
Article
Clinical Neurology
Bjorn Welzel, Ricardo Schmidt, Marie Johne, Wolfgang Loescher
Summary: In a rat model of birth asphyxia, midazolam not only prevented seizures but also reduced neuroinflammation, behavioral and cognitive abnormalities, and neurodegeneration following asphyxia. These findings suggest that midazolam has potential as an intervention to improve the treatment and outcome of birth asphyxia.
ANNALS OF NEUROLOGY
(2023)
Review
Clinical Neurology
Wolfgang Loescher, Carl E. Stafstrom
Summary: Epilepsy is associated with neurobehavioral comorbidities and a bidirectional relationship. Rodent models provide valuable insights into shared mechanisms and potential treatments for epilepsy and its comorbidities.
Article
Clinical Neurology
Chris Rundfeldt, Pavel Klein, Detlev Boison, Alexander Rotenberg, Raimondo D'Ambrosio, Cliff Eastman, Benton Purnell, Madhuvika Murugan, Howard P. Goodkin, Wolfgang Loescher
Summary: This study presents a novel meglumine-based solution of topiramate (TPM) that may be well suited for clinical development. Meglumine significantly enhances the aqueous solubility of TPM and can be used to prepare drug cocktails with other antiseizure medications. Tolerability studies demonstrate excellent tolerability of the novel drug solutions.
Review
Clinical Neurology
Wolfgang Loescher
Summary: Ivermectin is a potent antiparasitic drug, but it is not suitable for the treatment of epilepsy due to its limited penetration into the mammalian brain, non-selective activation of multiple receptors, equivocal preclinical evidence for antiseizure effects, and lack of direct antiseizure effect in clinical studies.
Article
Pharmacology & Pharmacy
Johannes A. Sake, Mohammed Ali Selo, Lyubomyr Burtnyak, Henriette E. Dahnhardt, Camelia Helbet, Severin Mairinger, Oliver Langer, Vincent P. Kelly, Carsten Ehrhardt
Summary: Multidrug resistance-associated protein 1 (MRP1/ABCC1) is an efflux transporter responsible for the extrusion of endogenous substances as well as xenobiotics and their respective metabolites. The generation of an ABCC1-/- clone based on the human distal lung epithelial cell line NCI-H441 via a targeted CRISPR/Cas9 approach provides a useful tool to study MRP1 function in vitro. The ABCC1-/- NCI-H441 clone showed complete absence of mRNA and protein, and retained the ability to form electrically tight barriers.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Adriana A. S. Tavares, Laura Mezzanotte, Wendy McDougald, Monique R. Bernsen, Christian Vanhove, Markus Aswendt, Giovanna D. Ielacqua, Felix Gremse, Carmel M. Moran, Geoff Warnock, Claudia Kuntner, Marc C. Huisman
Summary: This study surveyed and summarized the current status of preclinical imaging standardization through community survey and forum discussions. The results showed that there are still challenges in standardizing preclinical imaging techniques, with significant variations in data acquisition, processing, and reporting, and limited awareness of international guidelines for preclinical (imaging) research practices.
MOLECULAR IMAGING AND BIOLOGY
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Thomas Wanek, Severin Mairinger, Marco Raabe, Md Noor A. Alam, Thomas Filip, Johann Stanek, Gordon Winter, Lujuan Xu, Christian Laube, Tanja Weil, Volker Rasche, Claudia Kuntner
Summary: This study evaluated the biokinetics and biodistribution of 68Ga-radiolabelled NDs in a xenograft model. The results showed that the highest accumulation of labeled NDs was in the liver and spleen, while the tumor had a low radioactivity concentration.
NUCLEAR MEDICINE AND BIOLOGY
(2023)
Article
Microbiology
Irene Hernandez-Lozano, Severin Mairinger, Thomas Filip, Mathilde Loebsch, Johann Stanek, Claudia Kuntner, Martin Bauer, Markus Zeitlinger, Marcus Hacker, Thomas H. Helbich, Thomas Wanek, Oliver Langer
Summary: Transporter-mediated drug-drug interactions (DDIs) can have serious safety consequences in antimicrobial drug development. This study used PET imaging-based PK analysis to evaluate the effect of different drugs on the tissue distribution and excretion of [F-18]ciprofloxacin as a model drug. Results showed that pretreatment with probenecid and cimetidine significantly decreased the renal clearance of [F-18]ciprofloxacin. The study highlights the importance of PET imaging-based PK analysis in assessing transporter-mediated DDIs.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2023)
Article
Pharmacology & Pharmacy
Severin Mairinger, Irene Hernandez-Lozano, Thomas Filip, Mathilde Loebsch, Johann Stanek, Markus Zeitlinger, Marcus Hacker, Nicolas Tournier, Thomas Wanek, Carsten Ehrhardt, Oliver Langer
Summary: In this study, the influence of the membrane transporter P-glycoprotein (P-gp) on the pulmonary disposition of inhaled P-gp substrate drugs was investigated by conducting experiments on rats. The results indicate that the presence or absence of P-gp activity affects the lung retention of [11C]metoclopramide, leading to increased exposure in the lung due to decreased clearance into the blood.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Severin Mairinger, Irene Hernandez-Lozano, Lena Zachhuber, Thomas Filip, Mathilde Loebsch, Markus Zeitlinger, Marcus Hacker, Carsten Ehrhardt, Oliver Langer
Summary: This study used PET imaging to examine the impact of inhaled glucocorticoid budesonide on pulmonary MRP1 activity in rats. The results showed that inhaled budesonide had no significant effect on pulmonary MRP1 activity.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Review
Cell Biology
Wolfgang Loescher, H. Steve White
Summary: In the past 30 years, many new anti-seizure medicines have been developed for epilepsy treatment, but drug-resistant epilepsy (DRE) still affects a significant percentage of patients. Current approaches to discovering new DRE treatments involve testing drugs in preclinical models that show varying degrees of drug resistance. Recent efforts have been made to include more relevant models in the evaluation of investigational drugs, to better understand DRE mechanisms and test new therapies. This review discusses the pharmacology of different epilepsy models and the challenges in identifying novel treatments.
Article
Behavioral Sciences
Ricardo Schmidt, Bjorn Welzel, Wolfgang Loescher
Summary: Neonatal seizures are common after birth asphyxia, occurring more frequently in males. Stress and circadian rhythms also affect seizure characteristics.
EPILEPSY & BEHAVIOR
(2023)
Article
Optics
Keita Omiya, Markus Muller
Summary: We study the nature of the ergodicity-breaking quantum many-body scar states in the PXP model and reveal a common structure that gives rise to these states. We provide an extension of the PXP model that can host exact quantum scars and show that existing scar-stabilizing extensions can be understood within this framework. The exact scar states are obtained as large spin states of explicitly constructed pseudospins, and the quasiperiodic motion is shown to be the projection of the large pseudospin's precession onto the Rydberg-constrained subspace.