[18F]Amylovis as a Potential PET Probe for β-Amyloid Plaque: Synthesis, In Silico, In vitro and In vivo Evaluations
| العنوان: | [18F]Amylovis as a Potential PET Probe for β-Amyloid Plaque: Synthesis, In Silico, In vitro and In vivo Evaluations |
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| المؤلفون: | Geyla Dubed-Bandomo, Florencia Zoppolo, Samila León-Chaviano, Suchitil Rivera-Marrero, Alberto Bencomo-Martínez, Ingrid Kreimerman, Chryslaine Rodríguez-Tanty, Alejandro Perera-Pintado, Luis A. Espinosa-Rodríguez, Laura Fernandez-Maza, Laura Reyes, Marcin Balcerzyk, Daymara Mercerón-Martínez, Henry Engler, Marquiza Sablón-Carrazana, Eduardo Savio, Anaís Prats-Capote, Tania Pardo |
| المساهمون: | Ministerio de Ciencia, Tecnología y Medio Ambiente (Cuba), Consejo Superior de Investigaciones Científicas (España), Balcerzyk, Marcin, Balcerzyk, Marcin [0000-0001-6030-7416] |
| المصدر: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| بيانات النشر: | Bentham Science Publishers Ltd., 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Pharmacology, chemistry.chemical_classification, Positron emission tomography, Biodistribution, Chemistry, In silico, In vitro toxicology, Peptide, Blood–brain barrier, Molecular biology, Fluorine-18, In vitro, medicine.anatomical_structure, In vivo, Alzheimer’s disease diagnosis, medicine, Radiology, Nuclear Medicine and imaging, Senile plaques, Docking and dynamic simulations, β-amyloid probe, Iron cross-coupling reaction |
| الوصف: | [Background] Alzheimer’s disease (AD) is the most common form of dementia. Neuroimaging methods have widened the horizons for AD diagnosis and therapy. The goals of this work are the synthesis of 2-(3-fluoropropyl)-6-methoxynaphthalene (5) and its [18F]-radiolabeled counterpart ([18F]Amylovis), the in silico and in vitro comparative evaluations of [18F]Amylovis and [11C]Pittsburg compound B (PIB) and the in vivo preclinical evaluation of [18F]Amylovis in transgenic and wild mice. [Methods] Iron-catalysis cross coupling reaction, followed by fluorination and radiofluorination steps were carried out to obtain 5 and 18F-Amylovis. Protein/Aß plaques binding, biodistribution, PET/CT Imaging and immunohistochemical studies were conducted in healthy/transgenic mice. [Results] The synthesis of 5 was successful obtained. Comparative in silico studies predicting that 5 should have affinity to the Aβ-peptide, mainly through π-π interactions. According to a dynamic simulation study the ligand-Aβ peptide complexes are stable in simulation-time (ΔG = -5.31 kcal/mol). [18F]Amylovis was obtained with satisfactory yield, high radiochemical purity and specific activity. The [18F]Amylovis log Poct/PBS value suggests its potential ability for crossing the blood brain barrier (BBB). According to in vitro assays, [18F]Amylovis has an adequate stability in time. Higher affinity to Aβ plaques were found for [18F]Amylovis (Kd 0.16 nmol/L) than PIB (Kd 8.86 nmol/L) in brain serial sections of 3xTg-AD mice. Biodistribution in healthy mice showed that [18F]Amylovis crosses the BBB with rapid uptake (7 %ID/g at 5 min) and good washout (0.11±0.03 %ID/g at 60 min). Comparative PET dynamic studies of [18F]Amylovis in healthy and transgenic APPSwe/PS1dE9 mice, revealed a significant high uptake in the mice model. [Conclusion] The in silico, in vitro and in vivo results justify that [18F]Amylovis should be studied as a promissory PET imaging agent to detect the presence of Aβ senile plaques. This project was sponsored by Fondo Financiero de Ciencia e Innovación (FONCI) of Ministry of Science, Technology and Environment of Cuba (CITMA) Also, the present work was supported by the project I-LINK+ 0965 of the Consejo Superior de Investigaciones Científicas, Spain, and Cuba's National Science and Technology Program (PNCT, 31200). |
| تدمد: | 1874-4710 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::46296508080d3ecbd55db705fe4eb0b7 https://doi.org/10.2174/1874471012666190102165053 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....46296508080d3ecbd55db705fe4eb0b7 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 18744710 |
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