[18F]Flotaza for Aβ Plaque Diagnostic Imaging: Evaluation in Postmortem Human Alzheimer’s Disease Brain Hippocampus and PET/CT Imaging in 5xFAD Transgenic Mice

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(14), P. 7890 - 7890

Published: July 18, 2024

The diagnostic value of imaging Aβ plaques in Alzheimer's disease (AD) has accelerated the development fluorine-18 labeled radiotracers with a longer half-life for easier translation to clinical use. We have developed [

Language: Английский

---

Amyloid Β Fragments that Suppress Oligomers But Not Fibrils are Cytoprotective

Published: Jan. 1, 2025

Language: Английский

---

Towards Imaging Tau Hyperphosphorylation: Is DYRK1A a Potential Target for Imaging Hyperphosphorylation of Tau? Molecular Modeling Assessment and Synthesis of [125I]Radioiodinated DYRK1A Inhibitor

Molecules, Journal Year: 2025, Volume and Issue: 30(5), P. 990 - 990

Published: Feb. 21, 2025

Dual specificity tyrosine-phosphorylation regulated kinase 1A (DYRK1A), a phosphorylation kinase, is localized within the central nervous system and linked to hyperphosphorylation of Tau. Imaging DYRK1A may provide an earlier biomarker for Tauopathies, including Alzheimer’s disease (AD). We have used Chimera-Autodock evaluate potential molecules binding site DYRK1A. Five molecules, 10-bromo-2-iodo-11H-indolo[3,2-c]quinoline-6-carboxylic acid (4E3), 10-iodo-11H-indolo[3,2-c]quinoline-6-carboxylic (KuFal184), harmine, 6-(fluoro-3-(1H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine (MK-6240), 6-iodo-3-(1H-pyrrolo[2,3-c]pyridine-1-yl)isoquinoline (IPPI), were found energies −10.4, −10.1, −9.0, −9.1, −9.4 kcal/mole, respectively. Two 4E3 KuFal184, selective DYRK1A, while harmine also had monoamine oxidase A affinity, MK-6240 IPPI affinity Tau present in brain slices AD subject labeled with [125I]IPPI. KuFal184 no effect on [125I]IPPI, suggesting absence overlap two molecules. MK-6240, known agent was, however, able compete The suggest affinities approximately 80–100 nM, which insufficient serve as imaging agent. higher (6 nM DYRK1A) suggested that [125I]KuFal184 be Electrophilic radioiodination was synthesize modest yields (25%) high radiochemical purity (>95%). Preliminary studies showed some selectivity cortical grey matter regions containing

Language: Английский

---

Amyloid β fragments that suppress oligomers but not fibrils are cytoprotective

Archives of Biochemistry and Biophysics, Journal Year: 2025, Volume and Issue: unknown, P. 110386 - 110386

Published: March 1, 2025

Language: Английский

---

[18F]Mefway: Imaging Serotonin 5HT1A Receptors in Human Postmortem Alzheimer’s and Parkinson’s Disease Anterior Cingulate. Potential Applications to Human Positron Emission Tomography Studies

Biomolecules, Journal Year: 2025, Volume and Issue: 15(4), P. 592 - 592

Published: April 16, 2025

Serotonin 5HT1A receptors may be affected in neurodegeneration, such as Alzheimer’s disease (AD) and Parkinson’s (PD). Using the selective receptor positron emission tomography (PET) imaging agent, [18F]mefway, autoradiographic studies from postmortem human brains of AD, PD, cognitively normal (CN) subjects were carried out. Levels [18F]mefway binding compared with monoamine oxidase A (MAO-A) measured using [18F]FAZIN3 dopamine D2/D3 [18F]fallypride same subjects. Autoradiograms brain sections anterior cingulate corpus callosum CN, AD (n = 6 each group) analyzed. Significant increased was found (+30%) PD (+11%) to CN brains. This increase positively correlated binding, suggesting greater availability when MAO-A levels are higher. Differences three groups not significant. Our results support finding that is elevated cortex negatively MAO-A. upregulation potentially a response lower serotonin due activity this region or other neuroinflammatory changes. Thus, potential target for diagnostic therapeutic approaches PD.

Language: Английский

---

Radioiodinated Tau Imaging Agent III Molecular Modeling, Synthesis, and Evaluation of a New Tau Imaging Agent, [125I]ISAS in Post-Mortem Human Alzheimer’s Disease Brain

Molecules, Journal Year: 2024, Volume and Issue: 29(14), P. 3308 - 3308

Published: July 13, 2024

Using a molecular modeling approach for Tau-binding sites, we modified our previously reported imaging agent, [125I]INFT, the potential improvement of binding properties to Tau in an Alzheimer’s disease (AD) brain. Two new derivatives, namely [125I]ISAS and [125I]NIPZ, were designed, where energies at site 1 −7.4 −6.0 kcal/mole, respectively, compared [125I]INFT (−7.6 kcal/mole). The radiosynthesis [125I]NIPZ was carried out by using iodine-125 purified chromatographically achieve >90% purity. In vitro affinities (IC50) as follows: INFT = 7.3 × 10−8 M; ISAS 4.7 NIPZ > 10−6 M. gray matter (GM) correlated with presence AD brain, confirmed anti-Tau immunohistochemistry. did not bind Tau, similar levels observed GM white (WM). Four radiotracers rank order found be [125I]IPPI >>> GM/WM ratios 7.74 4.86 3.62 >> 1.24. predictive value Chimera–AutoDock structurally related compounds sites (measured energy) good. A energy less than −7 kcal/mole is necessary −8 will more suitable developing agents.

Language: Английский

---

A rapid and novel quantitative determination of Lecanemab monoclonal antibody for Alzheimer’s disease using reverse phase ultra performance liquid chromatography

Analytical Chemistry Letters, Journal Year: 2024, Volume and Issue: 14(4), P. 446 - 457

Published: July 3, 2024

Language: Английский

---