A5000124843- Adenosine and Purinergic Signaling
- Pharmacological Receptor Mechanisms and Effects
- Cancer Immunotherapy and Biomarkers
- Neuroscience and Neuropharmacology Research
- Receptor Mechanisms and Signaling
- Radiopharmaceutical Chemistry and Applications
- Medical Imaging Techniques and Applications
- Neuropeptides and Animal Physiology
- Peptidase Inhibition and Analysis
- Immune Cell Function and Interaction
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Inorganic Fluorides and Related Compounds
- Adipose Tissue and Metabolism
- Fluorine in Organic Chemistry
- Cardiovascular Disease and Adiposity
- Click Chemistry and Applications
- Viral Infections and Vectors
- Neuroinflammation and Neurodegeneration Mechanisms
- Cardiac Imaging and Diagnostics
- Chemical Synthesis and Analysis
- Mosquito-borne diseases and control
- Carbohydrate Chemistry and Synthesis
- Crystallization and Solubility Studies
- Immune cells in cancer
University of Virginia
2025
Singapore Bioimaging Consortium
2019-2024
Agency for Science, Technology and Research
2019-2024
Bangalore Medical College and Research Institute
2024
University of Oslo
2017-2019
Kjemi (Norway)
2017-2019
University Medical Center Groningen
2011-2017
University of Groningen
2011-2017
Radboud University Nijmegen
2017
We report a general method for the labeling of both CF3 and CF2 H groups in broad range chemical settings (aryl, oxide, sulfide). The utilizes frustrated Lewis pair mediated selective C-F activation to formally substitute fluorine-19 with fluorine-18 two-step defluorination/radiofluorination process, as such can utilize target compounds starting materials. radiotracer precursors be isolated stable salts prior radiofluorination. delivers good radiochemical yields molar activities (up 35.2±6.5...
Cerebral adenosine A2A receptors (A2ARs) are attractive therapeutic targets for the treatment of neurodegenerative and psychiatric disorders. We developed high affinity selective compound 8 (SCH442416) analogs as in vivo probes A2ARs using PET. observed A2AR-mediated accumulation [18F]fluoropropyl ([18F]-10b) [18F]fluoroethyl ([18F]-10a) derivatives brain. The striatum was clearly visualized PET vitro autoradiography images control animals no longer visible after pretreatment with A2AR...
2-(2-Furanyl)-7-[2-[4-[4-(2-[11C]methoxyethoxy)phenyl]-1-piperazinyl]ethyl]7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine-5-amine [11C]-3 ([11C]Preladenant) was developed for mapping cerebral adenosine A2A receptors (A2ARs) with PET. The tracer synthesized in high specific activity and purity. Tissue distribution studied by PET imaging, ex vivo biodistribution (BD), vitro autoradiography (ARG) experiments. Regional brain uptake of consistent known A2ARs distribution, highest striatum....
Abstract Purpose Chemotherapeutic adjuvants, such as oxaliplatin (OXA) and 5-fluorouracil (5-FU), that enhance the immune system, are being assessed strategies to improve durable response rates when used in combination with checkpoint inhibitor (ICI) monotherapy cancer patients. In this study, we explored granzyme B (GZB), released by tumor-associated cells, a PET imaging-based stratification marker for successful therapy using fluorine-18 ( 18 F)-labelled GZB peptide ([ F]AlF-mNOTA-GZP)....
The browning of white adipose tissue (WAT) into beige has been proposed as a strategy to enhance energy expenditure combat the growing epidemic obesity. Research strategies are hampered by lack sensitive, translatable, imaging tools capable detecting fat mass non-invasively. [18F]FDG is able detect activated but provides little information on unstimulated mass. We have assessed use [18F]FEPPA, tracer for TSPO-18KDa found outer mitochondrial membrane, an alternative agent brown (BAT) and fat....
[11C]Preladenant was developed as a novel adenosine A2A receptor positron emission tomography radioligand. The present study aims to evaluate the suitability of [11C]preladenant for quantification striatal density and assessment occupancy by KW-6002. Sixty- or ninety-minute dynamic imaging performed on rats. Tracer kinetics quantified two-tissue compartment model, Logan graphical analysis several reference tissue-based models. Test-retest reproducibility assessed repeated two consecutive...
Activation of adenosine A(1) receptors (A(1)R) in the brain causes sedation, reduces anxiety, inhibits seizures, and promotes neuroprotection. Cerebral A(1)R can be visualized using 8-dicyclopropylmethyl-1-(11)C-methyl-3-propyl-xanthine ((11)C-MPDX) PET. This study aims to test whether (11)C-MPDX used for quantitative studies cerebral rodents.(11)C-MPDX was injected (intravenously) into isoflurane-anesthetized male Wistar rats (300 g). A dynamic scan central nervous system obtained, a...
[11C]Preladenant was developed as a novel adenosine A2A receptor PET radioligand. The aim of this study to determine the radiation dosimetry [11C]preladenant and investigate whether estimation based on organ harvesting can be replaced by positron emission tomography (PET)/x-ray computed (CT) imaging in rats. Male Wistar rats (n = 35) were i.v. injected with [11C]preladenant. tracer biodistribution determined at 1, 5, 15, 30, 60, 90 min post injection. Hollow organs including stomach,...
Immune checkpoint inhibitors have shown great promise, emerging as a new pillar of treatment for cancer; however, only relatively small proportion recipients show durable response to treatment. Strategies that reliably differentiate durably-responding tumours from non-responsive are critical unmet need. Persistent and immunological responses associated with the generation memory T cells. Effector cells tumour immune therapies characterized by substantial upregulation potassium channel Kv1.3...
The cerebral adenosine A<sub>2A</sub> receptor is an attractive therapeutic target for neuropsychiatric disorders. <sup>18</sup>F-fluoroethyl and <sup>18</sup>F-fluoropropyl analogs of <sup>18</sup>F-labeled pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine (SCH442416) (<sup>18</sup>F-FESCH <sup>18</sup>F-FPSCH, respectively) were developed as receptor–specific PET ligands. Our aim was to determine appropriate compartmental model tracer kinetics, evaluate a reference tissue approach, select...
Adenosine A1 receptors (A1Rs) in human and rodent brains can be visualized with the radioligand 8-dicyclopropylmethyl-1-(11)C-methyl-3-propylxanthine ((11)C-MPDX) PET. Here we investigated whether A1R occupancy by nonradioactive agonists antagonists assessed this technique.Small-animal PET scans arterial blood sampling were obtained for 4 groups of isoflurane-anesthetized Wistar rats: controls (n = 7); pretreated a centrally active agonist, N(6)-cyclopentyladenosine (CPA; 0.25 mg/kg...
Imaging of the mu opioid receptor (MOR) availability with positron emission tomography (PET) is a pertinent challenge in Neuroscience. Both, regulation expression and occupancy by endogeneous opioids play into cognitive behavioral phenotypes healthy function disease. Receptor active inactive states can be measured using high affinity radioagonist radioantagonist PET tracers, respectively. Occupancy assessment requires radioligands showing competitive reversible binding moderate to MOR, which...
Protein-based 18F-PET tracers offer new possibilities in early disease detection and personalized medicine. Their development relies heavily on the availability effectiveness of 18F-prosthetic groups. We prepared evaluated a novel arginine-selective prosthetic group, 4-[18F]fluorophenylglyoxal ([18F]FPG). [18F]FPG was radiosynthesized by one-pot, two-step procedure with non-decay-corrected (n.d.c.) isolated radiochemical yield (RCY) 41 ± 8% (n = 10). constitutes generic tool for 18F-labeling...
Immune checkpoint inhibitors (ICIs) block receptors that tumours use for immune evasion, allowing cells to target and destroy cancer cells. Despite rapid advancements in immunotherapy, durable response rates ICIs remains low. To address this, combination clinical trials are underway assessing whether adjuvants can enhance responsiveness by increasing tumour immunogenicity. CpG-oligodeoxynucleotides (CpG-ODN) synthetic DNA fragments containing an unmethylated cysteine-guanosine motif...
O'nyong-nyong virus (ONNV) is an arthritogenic alphavirus that caused two large epidemics in 1959 and 1996, affecting millions of people Africa. More recently, sero-surveillance healthy blood donors conducted 2019 revealed high rates unreported ONNV infection Uganda. Due to similar clinical symptoms with other endemic mosquito-borne pathogens the region, including chikungunya virus, dengue malaria, infections are often un- or misdiagnosed. Elucidating immunopathogenic factors this...
Abstract Background Significant developments in stem cell therapy for Parkinson’s disease (PD) have already been achieved; however, methods reliable assessment of dopamine neuron maturation vivo are lacking. Establishing the efficacy new cellular therapies using non-invasive methodologies will be critical future regulatory approval and application. The current study examines utility neuroimaging to characterise maturation, innervation functional release transplanted human embryonic...
Often, patients fail to respond immune checkpoint inhibitor (ICI) treatment despite favourable biomarker status. Numerous chemotherapeutic agents have been shown promote tumour immunogenicity when used in conjunction with ICIs; however, little is known about whether such combination therapies lead a lasting response. Given the potential toxicity of ICI-chemotherapy combinations, identification biomarkers that accurately predict how individuals specific combinations and these responses will...
Browning of white adipose tissue (WAT) into beige adipocytes has been proposed as a strategy to tackle the ongoing obesity epidemic. Thermogenic stimuli have investigated with aim converting existing tissue, primarily used for energy storage, capable dissipating energy; however, evaluation is complicated by dearth noninvasive methodologies quantify de novo in WAT. Imaging [ 18 F]FDG commonly measure brown (BAT) and but relationship between adipocytes, thermogenesis uptake unclear. F]BCPP‐EF,...
The low response rates associated with immune checkpoint inhibitor (ICI) use has led to a surge in research investigating adjuvant combination strategies an attempt enhance efficacy. Repurposing existing drugs as adjuvants accelerates the pace of cancer therapy research; however, many combinations exacerbate immunogenic elicited by ICIs and can lead adverse immune-related events. Metformin, widely used type 2 diabetes drug is ideal candidate repurpose it good safety profile studies suggest...
The NR2B subunit of the N-methyl-d-aspartate (NMDA) receptor has been implicated in controlling synaptic plasticity, memory, and learning. Herein, we describe an 11C-labeled PET radiotracer based on 1-(4-chlorophenethyl)-6-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-ol, Ro04-5595. was evaluated rats using PET. study showed a good pharmacokinetic profile with rapid uptake washout over 90 min. Complementary high-resolution autoradiographic images [3H]Ro04-5595 demonstrated strong binding...