Seminars in Nuclear Medicine, Journal Year: 2023, Volume and Issue: 53(5), P. 555 - 557
Published: July 13, 2023
Language: Английский
Neurology International, Journal Year: 2024, Volume and Issue: 16(2), P. 419 - 431
Published: April 8, 2024
Therapeutic antibodies for reducing Aβ plaque load in Alzheimer’s disease (AD) is currently making rapid progress. The diagnostic imaging of AD has been underway and now used clinical studies. Here, we report our preliminary findings on a therapeutic antibody, Lecanemab, postmortem brain anterior cingulate. [125I]5-iodo-3-pyridinecarboxamido-Lecanemab ([125I]IPC-Lecanemab) was prepared by coupling N-succinimidyl-5-([125I]iodo)-3-pyridinecarboxylate with Lecanemab modest yields. distinct binding [125I]IPC-Lecanemab to Aβ-rich regions human brains higher grey matter (GM) containing plaques compared white (WM) (GM/WM 1.6). Anti-Aβ immunostaining correlated regional the brains. consistent small molecules, [18F]flotaza [125I]IBETA, same subjects. [18F]Flotaza however, exhibited significantly GM/WM ratios (>20) [125I]IPC-Lecanemab. Our results suggest that radiolabeled retains ability bind may therefore be useful as PET radiotracer when labeled [124I]IPC-Lecanemab. directly visualize vivo promising antibody treatment planning dosing could complimentary small-molecule assess outcomes interventions.
Language: Английский
Citations
7
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
Citations
6
TrAC Trends in Analytical Chemistry, Journal Year: 2024, Volume and Issue: 172, P. 117546 - 117546
Published: Jan. 17, 2024
Language: Английский
Citations
5
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
Citations
0
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
Citations
1
EJNMMI Radiopharmacy and Chemistry, Journal Year: 2024, Volume and Issue: 9(1)
Published: Dec. 23, 2024
Abstract Background The cannabinoid type 2 receptors (CB2R) represent a target of increasing importance in neuroimaging due to its upregulation under various neuropathological conditions. Previous evaluation [ 18 F]JHU94620 for the non-invasive assessment CB2R availability by positron emission tomography (PET) revealed favourable binding properties and brain uptake, however rapid metabolism, generation brain-penetrating radiometabolites have been main limitations. To reduce bias quantification blood–brain barrier (BBB)-penetrating radiometabolites, we aimed improve metabolic stability developing - d 4 8 deuterated isotopologues F]JHU94620. Results showed improved avoiding accumulation BBB-penetrating over time. CB2R-specific with K D values low nanomolar range was determined across species. Dynamic PET studies reversible uptake F]JHU94620- spleen local h CB2R(D80N) protein overexpression striatal region rats. Conclusion These results support further investigations pathological models tissues as prerequisite clinical translation.
Language: Английский
Citations
0
Seminars in Nuclear Medicine, Journal Year: 2023, Volume and Issue: 53(5), P. 555 - 557
Published: July 13, 2023
Language: Английский
Citations
0