17 results on '"Wuest, Frank"'
Search Results
2. PET Imaging of Fructose Metabolism in a Rodent Model of Neuroinflammation with 6-[ 18 F]fluoro-6-deoxy-D-fructose.
- Author
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Boyle, Amanda J., Murrell, Emily, Tong, Junchao, Schifani, Christin, Narvaez, Andrea, Wuest, Melinda, West, Frederick, Wuest, Frank, and Vasdev, Neil
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POSITRON emission tomography ,METABOLIC models ,FRUCTOSE ,NEUROINFLAMMATION ,MICROGLIA ,POLYETHYLENE terephthalate ,TRANSLOCATOR proteins - Abstract
Fluorine-18 labeled 6-fluoro-6-deoxy-D-fructose (6-[
18 F]FDF) targets the fructose-preferred facilitative hexose transporter GLUT5, which is expressed predominantly in brain microglia and activated in response to inflammatory stimuli. We hypothesize that 6-[18 F]FDF will specifically image microglia following neuroinflammatory insult. 6-[18 F]FDF and, for comparison, [18 F]FDG were evaluated in unilateral intra-striatal lipopolysaccharide (LPS)-injected male and female rats (50 µg/animal) by longitudinal dynamic PET imaging in vivo. In LPS-injected rats, increased accumulation of 6-[18 F]FDF was observed at 48 h post-LPS injection, with plateaued uptake (60–120 min) that was significantly higher in the ipsilateral vs. contralateral striatum (0.985 ± 0.047 and 0.819 ± 0.033 SUV, respectively; p = 0.002, n = 4M/3F). The ipsilateral–contralateral difference in striatal 6-[18 F]FDF uptake expressed as binding potential (BPSRTM ) peaked at 48 h (0.19 ± 0.11) and was significantly decreased at one and two weeks. In contrast, increased [18 F]FDG uptake in the ipsilateral striatum was highest at one week post-LPS injection (BPSRTM = 0.25 ± 0.06, n = 4M). Iba-1 and GFAP immunohistochemistry confirmed LPS-induced activation of microglia and astrocytes, respectively, in ipsilateral striatum. This proof-of-concept study revealed an early response of 6-[18 F]FDF to neuroinflammatory stimuli in rat brain. 6-[18 F]FDF represents a potential PET radiotracer for imaging microglial GLUT5 density in brain with applications in neuroinflammatory and neurodegenerative diseases. [ABSTRACT FROM AUTHOR]- Published
- 2022
- Full Text
- View/download PDF
3. Good practices for 68Ga radiopharmaceutical production.
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Nelson, Bryce J. B., Andersson, Jan D., Wuest, Frank, and Spreckelmeyer, Sarah
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RADIOACTIVE tracers ,CYCLOTRONS ,PROSTATE ,RADIOACTIVE decay ,POSITRON emission tomography ,RADIOPHARMACEUTICALS ,BEST practices ,TUMOR markers - Abstract
Background: The radiometal gallium-68 (
68 Ga) is increasingly used in diagnostic positron emission tomography (PET), with68 Ga-labeled radiopharmaceuticals developed as potential higher-resolution imaging alternatives to traditional99m Tc agents. In precision medicine, PET applications of68 Ga are widespread, with68 Ga radiolabeled to a variety of radiotracers that evaluate perfusion and organ function, and target specific biomarkers found on tumor lesions such as prostate-specific membrane antigen, somatostatin, fibroblast activation protein, bombesin, and melanocortin. Main body: These68 Ga radiopharmaceuticals include agents such as [68 Ga]Ga-macroaggregated albumin for myocardial perfusion evaluation, [68 Ga]Ga-PLED for assessing renal function, [68 Ga]Ga-t-butyl-HBED for assessing liver function, and [68 Ga]Ga-PSMA for tumor imaging. The short half-life, favourable nuclear decay properties, ease of radiolabeling, and convenient availability through germanium-68 (68 Ge) generators and cyclotron production routes strongly positions68 Ga for continued growth in clinical deployment. This progress motivates the development of a set of common guidelines and standards for the68 Ga radiopharmaceutical community, and recommendations for centers interested in establishing68 Ga radiopharmaceutical production. Conclusion: This review outlines important aspects of68 Ga radiopharmacy, including68 Ga production routes using a68 Ge/68 Ga generator or medical cyclotron, standardized68 Ga radiolabeling methods, quality control procedures for clinical68 Ga radiopharmaceuticals, and suggested best practices for centers with established or upcoming68 Ga radiopharmaceutical production. Finally, an outlook on68 Ga radiopharmaceuticals is presented to highlight potential challenges and opportunities facing the community. [ABSTRACT FROM AUTHOR]- Published
- 2022
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4. Simultaneous PET/MRI: The future gold standard for characterizing motor neuron disease--A clinico-radiological and neuroscientific perspective.
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Juengling, Freimut D., Wuest, Frank, Kalra, Sanjay, Agosta, Federica, Schirrmacher, Ralf, Thiel, Alexander, Thaiss, Wolfgang, Müller, Hans-Peter, and Kassubek, Jan
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MOTOR neuron diseases ,GOLD futures ,AMYOTROPHIC lateral sclerosis ,MAGNETIC resonance imaging ,POSITRON emission tomography - Abstract
Neuroimaging assessment of motor neuron disease has turned into a cornerstone of its clinical workup. Amyotrophic lateral sclerosis (ALS), as a paradigmatic motor neuron disease, has been extensively studied by advanced neuroimaging methods, including molecular imaging by MRI and PET, furthering finer and more specific details of the cascade of ALS neurodegeneration and symptoms, facilitated by multicentric studies implementing novel methodologies. With an increase in multimodal neuroimaging data on ALS and an exponential improvement in neuroimaging technology, the need for harmonization of protocols and integration of their respective findings into a consistent model becomes mandatory. Integration of multimodal data into a model of a continuing cascade of functional loss also calls for the best attempt to correlate the different molecular imaging measurements as performed at the shortest inter-modality time intervals possible. As outlined in this perspective article, simultaneous PET/MRI, nowadays available at many neuroimaging research sites, offers the perspective of a one-stop shop for reproducible imaging biomarkers on neuronal damage and has the potential to become the new gold standard for characterizing motor neuron disease from the clinico-radiological and neuroscientific perspectives. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
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5. Fluorine-18 Labelled Radioligands for PET Imaging of Cyclooxygenase-2.
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Kaur, Jatinder, Bhardwaj, Atul, and Wuest, Frank
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CYCLOOXYGENASE 2 ,POSITRON emission tomography ,CYCLOOXYGENASE 2 inhibitors ,MOLECULAR probes ,DIAGNOSTIC imaging ,EARLY detection of cancer - Abstract
Molecular imaging probes enable the early and accurate detection of disease-specific biomarkers and facilitate personalized treatment of many chronic diseases, including cancer. Among current clinically used functional imaging modalities, positron emission tomography (PET) plays a significant role in cancer detection and in monitoring the response to therapeutic interventions. Several preclinical and clinical studies have demonstrated the crucial involvement of cyclooxygenase-2 (COX-2) isozyme in cancer development and progression, making COX-2 a promising cancer biomarker. A variety of COX-2-targeting PET radioligands has been developed based on anti-inflammatory drugs and selective COX-2 inhibitors. However, many of those suffer from non-specific binding and insufficient metabolic stability. This article highlights examples of COX-2-targeting PET radioligands labelled with the short-lived positron emitter
18 F, including radiosynthesis and PET imaging studies published in the last decade (2012–2021). [ABSTRACT FROM AUTHOR]- Published
- 2022
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6. Synthesis of a 2-nitroimidazole derivative N-(4-[18F]fluorobenzyl)-2-(2-nitro-1H-imidazol-1-yl)-acetamide ([18 F]FBNA) as PET radiotracer for imaging tumor hypoxia.
- Author
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Nario, Arian Pérez, Woodfield, Jenilee, dos Santos, Sofia Nascimento, Bergman, Cody, Wuest, Melinda, Araújo, Yasniel Babí, Lapolli, André Luis, West, Frederick G., Wuest, Frank, and Bernardes, Emerson Soares
- Subjects
ACETAMIDE ,POSITRON emission tomography ,HYPOXEMIA ,RADIOCHEMICAL purification ,TUMOR microenvironment ,RADIOACTIVE tracers - Abstract
Background: Tissue hypoxia is a pathological condition characterized by reducing oxygen supply. Hypoxia is a hallmark of tumor environment and is commonly observed in many solid tumors. Non-invasive imaging techniques like positron emission tomography (PET) are at the forefront of detecting and monitoring tissue hypoxia changes in vivo. Results: We have developed a novel
18 F-labeled radiotracer for hypoxia PET imaging based on cytotoxic agent benznidazole. Radiotracer N-(4-[18 F]fluorobenzyl)-2-(2-nitro-1H-imidazol-1-yl)acetamide ([18 F]FBNA) was synthesized through acylation chemistry with readily available 4-[18 F]fluorobenzyl amine. Radiotracer [18 F]FBNA was obtained in good radiochemical yields (47.4 ± 5.3%) and high radiochemical purity (> 95%). The total synthesis time was 100 min, including HPLC purification and the molar activity was greater than 40 GBq/µmol. Radiotracer [18 F]FBNA was stable in saline and mouse serum for 6 h. [18 F]FBNA partition coefficient (logP = 1.05) was found to be more lipophilic than [18 F]EF-5 (logP = 0.75), [18 F]FMISO (logP = 0.4) and [18 F]FAZA (logP = − 0.4). In vitro studies showed that [18 F]FBNA accumulates in gastric cancer cell lines AGS and MKN45 under hypoxic conditions. Conclusions: Hence, [18 F]FBNA represents a novel and easy-to-prepare PET radioligand for imaging hypoxia. [ABSTRACT FROM AUTHOR]- Published
- 2022
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7. Dual Probes for Positron Emission Tomography (PET) and Fluorescence Imaging (FI) of Cancer.
- Author
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Yuen, Richard, West, Frederick G., and Wuest, Frank
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FLUORESCENCE ,POSITRON emission tomography ,MOLECULAR probes ,PETS ,SURGICAL excision ,INDIVIDUALIZED medicine - Abstract
Simple Summary: Being able to detect and image tumors is extremely important for proper diagnosis and treatment. The most sensitive technique, positron emission tomography (PET), is widely applied for such a purpose. Additionally, fluorescence imaging can be used to visually see the margins between healthy and cancerous tissue during surgery. These two techniques can be combined to optimize patient outcomes by ensuring maximum tumor removal. This review will discuss the work that has been done recently to combine these two imaging capabilities into one imaging agent. Dual probes that possess positron emission tomography (PET) and fluorescence imaging (FI) capabilities are precision medicine tools that can be used to improve patient care and outcomes. Detecting tumor lesions using PET, an extremely sensitive technique, coupled with fluorescence-guided surgical resection of said tumor lesions can maximize the removal of cancerous tissue. The development of novel molecular probes is important for targeting different biomarkers as every individual case of cancer has different characteristics. This short review will discuss some aspects of dual PET/FI probes and explore the recently reported examples. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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8. Identify. Quantify. Predict. Why Immunologists Should Widely Use Molecular Imaging for Coronavirus Disease 2019.
- Author
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Juengling, Freimut D., Maldonado, Antonio, Wuest, Frank, and Schindler, Thomas H.
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COVID-19 ,IMMUNOLOGISTS ,GLUCOSE metabolism disorders ,NANOTECHNOLOGY ,POSITRON emission tomography - Abstract
Molecular imaging using PET/CT or PET/MRI has evolved from an experimental imaging modality at its inception in 1972 to an integral component of diagnostic procedures in oncology, and, to lesser extent, in cardiology and neurology, by successfully offering in-vivo imaging and quantitation of key pathophysiological targets or molecular signatures, such as glucose metabolism in cancerous disease. Apart from metabolism probes, novel radiolabeled peptide and antibody PET tracers, including radiolabeled monoclonal antibodies (mAbs) have entered the clinical arena, providing the in-vivo capability to collect target-specific quantitative in-vivo data on cellular and molecular pathomechanisms on a whole-body scale, and eventually, extract imaging biomarkers possibly serving as prognostic indicators. The success of molecular imaging in mapping disease severity on a whole-body scale, and directing targeted therapies in oncology possibly could translate to the management of Coronavirus Disease 2019 (COVID-19), by identifying, localizing, and quantifying involvement of different immune mediated responses to the infection with SARS-COV2 during the course of acute infection and possible, chronic courses with long-term effects on specific organs. The authors summarize current knowledge for medical imaging in COVID-19 in general with a focus on molecular imaging technology and provide a perspective for immunologists interested in molecular imaging research using validated and immediately available molecular probes, as well as possible future targets, highlighting key targets for tailored treatment approaches as brought up by key opinion leaders. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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9. Synthesis of 2-Fluoroacetoacetic Acid and 4-Fluoro-3-hydroxy-butyric Acid.
- Author
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Mattingly, Stephanie J., Wuest, Frank, and Schirrmacher, Ralf
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3-Hydroxybutyric acid ,ACETOACETIC acid ,POSITRON emission tomography ,NUCLEAR magnetic resonance ,BUTYRIC acid ,FLUORINE isotopes - Abstract
The butyric acid scaffold is the base structure of several human metabolites that serve diverse and prominent biochemical roles including as oxidative sources of cellular energy and as substrates for biosynthesis. Derivatization of metabolites through incorporation of fluorine often alters bioactivity and can facilitate detection and analysis by nuclear magnetic resonance or positron emission tomography depending upon the fluorine isotope employed. We describe the synthesis of two new fluorinated butyric acids (and three related esters) that are derivatives of the metabolites acetoacetic acid and 3-hydroxybutyric acid. 4-Fluoro-3-hydroxybutyric acid is prepared from epoxy ester precursors via ring opening by triethylamine trihydrofluoride. 2-Fluoroacetoacetic acid is prepared by electrophilic fluorination of an acid-labile β-keto ester. The gradual pH-dependent decarboxylation of 2-fluoroacetoacetic acid is investigated by
19 F NMR spectroscopy. [ABSTRACT FROM AUTHOR]- Published
- 2019
- Full Text
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10. Targeting Prostate-Specific Membrane Antigen (PSMA) with F-18-Labeled Compounds: the Influence of Prosthetic Groups on Tumor Uptake and Clearance Profile.
- Author
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Bouvet, Vincent, Wuest, Melinda, Bailey, Justin, Bergman, Cody, Janzen, Nancy, Valliant, John, Wuest, Frank, Bailey, Justin J, and Valliant, John F
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DIAGNOSIS ,PROSTATE cancer ,PROSTATE-specific membrane antigen ,POSITRON emission tomography ,FLUORODEOXYGLUCOSE F18 ,BIOMARKERS ,RADIOACTIVE tracers ,ANIMAL experimentation ,CELL lines ,FLUORINE isotopes ,MICE ,PROSTATE tumors ,RADIOISOTOPES ,TIME - Abstract
Purpose: Prostate-specific membrane antigen (PSMA) is an important biomarker expressed in the majority of prostate cancers. The favorable positron emission tomography (PET) imaging profile of the PSMA imaging agent 2-(3-(1-carboxy-5-[(6-[18F]fluoro-pyridine-3-carbonyl)-amino]-pentyl)-ureido)-pentane-dioic acid [18F]DCFPyL in preclinical prostate cancer models and in prostate cancer patients stimulated the development and validation of other fluorine-containing PSMA inhibitors to further enhance pharmacokinetics and simplify production methods. Here, we describe the synthesis and radiopharmacological evaluation of various F-18-labeled PSMA inhibitors which were prepared through different prosthetic group chemistry strategies.Procedures: Prosthetic groups N-succinimidyl-4-[18F]fluorobenzoate ([18F]SFB), 4-[18F]fluorobenzaldehyde, and 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) were used for bioconjugation reactions to PSMA-binding lysine-urea-glutamate scaffold via acylation and oxime formation. All fluorine-containing PSMA inhibitors were tested for their PSMA inhibitory potency in an in vitro competitive binding assay in comparison to an established reference compound [125I]TAAG-PSMA. Tumor uptake and clearance profiles of three F-18-labeled PSMA inhibitors ([18F]4, [18F]7, and [18F]8) were studied with dynamic PET imaging using LNCaP tumor-bearing mice.Results: F-18-labeled PSMA inhibitors were synthesized in 32-69 % radiochemical yields using (1) acylation reaction at the primary amino group of the lysine residue with [18F]SFB and (2) oxime formation with 4-[18F]fluorobenzaldehyde and [18F]FDG using the respective aminooxy-functionalized lysine residue. Compound 7 displayed an IC50 value of 6 nM reflecting very high affinity for PSMA. Compounds 4 and 8 showed IC50 values of 13 and 62 nM, respectively. The IC50 value of reference compound DCFPyL was 13 nM. Dynamic PET imaging revealed the following SUV60min for radiotracer uptake in PSMA(+) LNCaP tumors: 0.98 ([18F]DCFPyL), 2.11 ([18F]7), 0.40 ([18F]4), and 0.19 ([18F]8).Conclusion: The observed tumor uptake and clearance profiles demonstrate the importance of the selected prosthetic group on the pharmacokinetic profile of analyzed PSMA-targeting radiotracers. Radiotracer [18F]7 displayed the highest uptake and retention in LNCaP tumors, which exceeded uptake values of reference compound [18F]DCFPyL by more than 100 %. Despite the higher kidney and liver uptake and retention of compound [18F]7, the simple radiosynthesis and the exceptionally high tumor uptake (SUV60min 2.11) and retention make radiotracer [18F]7 an interesting alternative to radiotracer [18F]DCFPyL for PET imaging of PSMA in prostate cancer. [ABSTRACT FROM AUTHOR]- Published
- 2017
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11. Automated synthesis of [F]DCFPyL via direct radiofluorination and validation in preclinical prostate cancer models.
- Author
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Bouvet, Vincent, Wuest, Melinda, Jans, Hans-Soenke, Janzen, Nancy, Genady, Afaf, Valliant, John, Benard, Francois, and Wuest, Frank
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PROSTATE-specific membrane antigen ,RADIOACTIVE tracers ,PROSTATE cancer ,POSITRON emission tomography ,RADIOPHARMACOLOGY - Abstract
Background: Prostate-specific membrane antigen (PSMA) is frequently overexpressed and upregulated in prostate cancer. To date, various F- and Ga-labeled urea-based radiotracers for PET imaging of PSMA have been developed and entered clinical trials. Here, we describe an automated synthesis of [F]DCFPyL via direct radiofluorination and validation in preclinical models of prostate cancer. Methods: [F]DCFPyL was synthesized via direct nucleophilic heteroaromatic substitution reaction in a single reactor TRACERlab FX automated synthesis unit. Radiopharmacological evaluation of [F]DCFPyL involved internalization experiments, dynamic PET imaging in LNCaP (PSMA+) and PC3 (PSMA−) tumor-bearing BALB/c nude mice, biodistribution studies, and metabolic profiling. In addition, reversible two-tissue compartmental model analysis was used to quantify pharmacokinetics of [F]DCFPyL in LNCaP and PC3 tumor models. Results: Automated radiosynthesis afforded radiotracer [F]DCFPyL in decay-corrected radiochemical yields of 23 ± 5 % ( n = 10) within 55 min, including HPLC purification. Dynamic PET analysis revealed rapid and high uptake of radioactivity (SUV 0.95) in LNCaP tumors which increased over time (SUV 1.1). Radioactivity uptake in LNCaP tumors was blocked in the presence of nonradioactive DCFPyL (SUV 0.22). The muscle as reference tissue showed rapid and continuous clearance over time (SUV 0.06). Fast blood clearance of radioactivity resulted in tumor-blood ratios of 1.0 after 10 min and 8.3 after 60 min. PC3 tumors also showed continuous clearance of radioactivity over time (SUV 0.11). Kinetic analysis of PET data revealed the two-tissue compartmental model as best fit with K = 0.12, k = 0.18, k = 0.08, and k = 0.004 min, confirming molecular trapping of [F]DCFPyL in PSMA+ LNCaP cells. Conclusions: [F]DCFPyL can be prepared for clinical applications simply and in good radiochemical yields via a direct radiofluorination synthesis route in a single reactor automated synthesis unit. Radiopharmacological evaluation of [F]DCFPyL confirmed high PSMA-mediated tumor uptake combined with superior clearance parameters. Compartmental model analysis points to a two-step molecular trapping mechanism based on PSMA binding and subsequent internalization leading to retention of radioactivity in PSMA+ LNCaP tumors. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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12. PET imaging of cyclooxygenase-2 (COX-2) in a pre-clinical colorectal cancer model.
- Author
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Tietz, Ole, Wuest, Melinda, Marshall, Alison, Glubrecht, Darryl, Hamann, Ingrit, Wang, Monica, Bergman, Cody, Way, Jenilee, and Wuest, Frank
- Subjects
COLON cancer treatment ,CYCLOOXYGENASES ,CELL lines ,POSITRON emission tomography ,CHEMOPREVENTION - Abstract
Background: Cyclooxygenase-2 (COX-2) is the inducible isoform of the cyclooxygenase enzyme family. COX-2 is involved in tumor development and progression, and frequent overexpression of COX-2 in a variety of human cancers has made COX-2 an important drug target for cancer treatment. Non-invasive imaging of COX-2 expression in cancer would be useful for assessing COX-2-mediated effects on chemoprevention and radiosensitization using COX-2 inhibitors as an emerging class of anti-cancer drugs, especially for colorectal cancer. Herein, we describe the radiopharmacological analysis of [F]Pyricoxib, a novel radiolabeled COX-2 inhibitor, for specific PET imaging of COX-2 in colorectal cancer. Methods: Uptake of [F]Pyricoxib was assessed in human colorectal cancer cell lines HCA-7 (COX-2 positive) and HCT-116 (COX-2 negative). Standard COX-2 inhibitors were used to test for specificity of [F]Pyricoxib for COX-2 binding in vitro and in vivo. PET imaging, biodistribution, and radiometabolite analyses were included into radiopharmacological evaluation of [F]Pyricoxib. Results: Radiotracer uptake in COX-2 positive HCA-7 cells was significantly higher than in COX-2 negative HCT-116 cells ( P < 0.05). COX-2 inhibitors, celecoxib, rofecoxib, and SC58125, blocked uptake of [F]Pyricoxib in HCA-7 cells in a concentration-dependent manner. The radiotracer was slowly metabolized in mice, with approximately 60 % of intact compound after 2 h post-injection. Selective COX-2-mediated tumor uptake of [F]Pyricoxib in HCA-7 xenografts was confirmed in vivo. Celecoxib (100 mg/kg) selectively blocked tumor uptake by 16 % (PET image analysis; P < 0.05) and by 51 % (biodistribution studies; P < 0.01). Conclusions: The novel PET radiotracer [F]Pyricoxib displays a promising radiopharmacological profile to study COX-2 expression in cancer in vivo. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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- View/download PDF
13. Sonogashira cross-coupling reaction with 4-[18F]fluoroiodobenzene for rapid 18F-labelling of peptides.
- Author
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Way, Jenilee D., Bergman, Cody, and Wuest, Frank
- Subjects
COUPLING reactions (Chemistry) ,SONOGASHIRA reaction ,PEPTIDES ,IODOBENZENE ,RADIOLABELING ,FLUOROBENZENE ,POSITRON emission tomography - Abstract
The study describes the Sonogashira cross-coupling reaction with 4-[
18 F]fluoroiodobenzene ([18 F]FIB) as novel and efficient method for rapid labelling of peptides with the short-lived positron emitter fluorine-18. [ABSTRACT FROM AUTHOR]- Published
- 2015
- Full Text
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14. Synthesis, characterisation and evaluation of a novel copper-64 complex with selective uptake in EMT-6 cells under hypoxic conditions.
- Author
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Knight, James C., Wuest, Melinda, Saad, Fawaz A., Wang, Monica, Chapman, David W., Jans, Hans-Soenke, Lapi, Suzanne E., Kariuki, Benson M., Amoroso, Angelo J., and Wuest, Frank
- Subjects
COPPER research ,DIAGNOSTIC imaging ,POSITRON emission tomography ,CHELATING agents ,X-ray crystallography ,LABORATORY mice - Abstract
The radiometal
64 Cu is now widely used in the development of diagnostic imaging agents for positron emission tomography (PET). The present study has led to the development and evaluation of a novel chelating agent for64 Cu: the new monothiourea tripodal ligand 1-benzoyl-3-{6-[(bis-pyridin-2-ylmethyl-amino)-methyl]-pyridin-2-yl}-thiourea (MTUBo). X-ray crystallographic analysis has shown this ligand forms a mononuclear complex with copper(ii) and co-ordinates via a trigonal bipyramidal N4 S array of donor atoms. Promisingly, cell uptake studies revealed that64 Cu-MTUBo selectively accumulates in EMT-6 cells incubated under hypoxic conditions which may result from its relatively high CuII/I redox potential. Small-animal PET imaging and ex vivo biodistribution studies in EMT-6 tumor bearing BALB/c mice revealed significant tumor uptake after 1 h p.i., yielding tumor-to-muscle (T/M) and tumor-to-blood (T/B) ratios of 8.1 and 1.1, respectively. However, injection of64 Cu-acetate resulted in similar uptake indicating that the observed uptake was most likely non-specific. Despite showing high in vitro stability, it is likely that in vivo the complex undergoes transchelation to proteins within the blood in a relatively short timeframe. For comparison, the hypoxia imaging agent64 Cu-ATSM was also evaluated in the same murine tumor model and showed about 60% higher tumor uptake than64 Cu-MTUBo. [ABSTRACT FROM AUTHOR]- Published
- 2013
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15. Advances in [ 18 F]Trifluoromethylation Chemistry for PET Imaging.
- Author
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Francis, Felix and Wuest, Frank
- Subjects
POSITRON emission tomography ,RADIOACTIVE tracers ,RADIOCHEMICAL purification ,DIAGNOSTIC imaging ,MEDICAL research ,PHARMACEUTICAL chemistry - Abstract
Positron emission tomography (PET) is a preclinical and clinical imaging technique extensively used to study and visualize biological and physiological processes in vivo. Fluorine-18 (
18 F) is the most frequently used positron emitter for PET imaging due to its convenient 109.8 min half-life, high yield production on small biomedical cyclotrons, and well-established radiofluorination chemistry. The presence of fluorine atoms in many drugs opens new possibilities for developing radioligands labelled with fluorine-18. The trifluoromethyl group (CF3 ) represents a versatile structural motif in medicinal and pharmaceutical chemistry to design and synthesize drug molecules with favourable pharmacological properties. This fact also makes CF3 groups an exciting synthesis target from a PET tracer discovery perspective. Early attempts to synthesize [18 F]CF3 -containing radiotracers were mainly hampered by low radiochemical yields and additional challenges such as low radiochemical purity and molar activity. However, recent innovations in [18 F]trifluoromethylation chemistry have significantly expanded the chemical toolbox to synthesize fluorine-18-labelled radiotracers. This review presents the development of significant [18 F]trifluoromethylation chemistry strategies to apply [18 F]CF3 -containing radiotracers in preclinical and clinical PET imaging studies. The continuous growth of PET as a crucial functional imaging technique in biomedical and clinical research and the increasing number of CF3 -containing drugs will be the primary drivers for developing novel [18 F]trifluoromethylation chemistry strategies in the future. [ABSTRACT FROM AUTHOR]- Published
- 2021
- Full Text
- View/download PDF
16. Iodine-124: A Promising Positron Emitter for Organic PET Chemistry.
- Author
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Koehler, Lena, Gagnon, Katherine, McQuarrie, Steve, and Wuest, Frank
- Subjects
BIOACTIVE compounds ,IODINE spectra ,POSITRON emission tomography ,MOLECULAR microbiology ,MOLECULAR biology ,BIOCHEMISTRY ,NUCLEAR medicine ,RADIOISOTOPES ,CHEMICAL biology - Abstract
The use of radiopharmaceuticals for molecular imaging of biochemical and physiological processes in vivo has evolved into an important diagnostic tool in modern nuclear medicine and medical research. Positron emission tomography (PET) is currently the most sophisticated molecular imaging methodology, mainly due to the unrivalled high sensitivity which allows for the studying of biochemistry in vivo on the molecular level. The most frequently used radionuclides for PET have relatively short half-lives (e.g.
11 C: 20.4 min;18 F: 109.8 min) which may limit both the synthesis procedures and the time frame of PET studies. Iodine-124 (124 I, t1/2 = 4.2 d) is an alternative long-lived PET radionuclide attracting increasing interest for long term clinical and small animal PET studies. The present review gives a survey on the use of 124I as promising PET radionuclide for molecular imaging. The first part describes the production of124 I. The second part covers basic radiochemistry with124 I focused on the synthesis of124 I-labeled compounds for molecular imaging purposes. The review concludes with a summary and an outlook on the future prospective of using the long-lived positron emitter124 I in the field of organic PET chemistry and molecular imaging. [ABSTRACT FROM AUTHOR]- Published
- 2010
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17. Cell Cycle Regulating Kinase Cdk4 as a Potential Target for Tumor Cell Treatment and Tumor Imaging.
- Author
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Graf, Franziska, Koehler, Lena, Kniess, Torsten, Wuest, Frank, Mosch, Birgit, and Pietzsch, Jens
- Subjects
CYCLIN-dependent kinases ,CELL cycle ,CANCER treatment ,CELL proliferation ,POSITRON emission tomography ,TUMOR treatment ,RADIOISOTOPES in pharmacology ,RETINOBLASTOMA ,ANTINEOPLASTIC agents - Abstract
The cyclin-dependent kinase (Cdk)-cyclin D/retinoblastoma (pRb)/E2F cascade, which controls the G1/S transition of cell cycle, has been found to be altered in many neoplasias. Inhibition of this pathway by using, for example, selective Cdk4 inhibitors has been suggested to be a promising approach for cancer therapy. We hypothesized that appropriately radiolabeled Cdk4 inhibitors are suitable probes for tumor imaging and may be helpful studying cell proliferation processes in vivo by positron emission tomography. Herein, we report the synthesis and biological, biochemical, and radiopharmacological characterizations of two
124 I-labeled small molecule Cdk4 inhibitors (8-cyclopentyl-6-iodo-5-methyl-2-(4-piperazin-1-ylphenylamino)-8H-pyrido[2,3-d]-pyrimidin-7-one (CKIA) and 8-cyclopentyl-6-iodo-5-methyl-2-(5-(piperazin-1-yl)-pyridin-2- yl-amino)-8H-pyrido[2,3-d]pyrimidin-7-one (CKIB)). Our data demonstrate a defined and specific inhibition of tumor cell proliferation through CKIA and CKIB by inhibition of the Cdk4/pRb/E2F pathway emphasizing potential therapeutic benefit of CKIA and CKIB. Furthermore, radiopharmacological properties of [124 I]CKIA and [124 I]CKIB observed in human tumor cells are promising prerequisites for in vivo biodistribution and imaging studies. [ABSTRACT FROM AUTHOR]- Published
- 2009
- Full Text
- View/download PDF
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