Design and Evaluation of a Chalcone-Based Dimeric Scaffold Targeting Amyloid-Beta Plaques for Early Detection of Alzheimer’s Disease: Synthesis, Radiolabeling, In Vivo Studies, and Integrated Molecular Docking and Dynamics Simulation
6 affiliations
- 1Department of Nuclear Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
- 2Research Center for Nuclear Medicine, Tehran University of Medical Sciences, Tehran, Iran
- 3Department of Mechanical Engineering, Shiraz University of Technology, Shiraz, Iran
- 4Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
- 5Toxicology and Poisoning Research Centre, Tehran University of Medical Sciences, Tehran, Iran
- 6Department of Neurosciences and Addiction Studies, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
Abstract
Purpose:: Amyloid-Beta (Aβ) plaque imaging can serve as a desirable tool for early detection of Alzheimer’s disease (AD). This study presents a new dimer of a chalcone-based scaffold, [68Ga]Ga-DTPA[Ch-DE]2, as a potential radiotracer for Aβ plaques imaging.
Methods:: The synthesis of DTPA[Ch-DE]2 and its radiolabeling with gallium-68 were characterized using techniques such as 1H-NMR, mass spectrometry, HPLC, and instant thin-layer chromatography. Neurotoxicity of DTPA[Ch-DE]2 was evaluated using the MTT assay. The stability of radiotracer was tested in various buffer systems and human serum albumin (HSA). The binding affinity of the radiotracer to Aβ aggregations was evaluted on the brain sections from both normal and AD rat models. Positron emission tomography-computed tomography (PET/CT) of brain imaging and Thioflavin S staining characterized the AD model. Biodistribution studies and PET/CT scans were performed on normal and AD rats. Computational studies also were conducted.
Results:: [68Ga]Ga-DTPA[Ch-DE]2 was synthesized with over 93% radiochemical purity. It showed high stability in various buffer systems and HSA after 2 hours. The binding assay revealed strong affinity to Aβ42 aggregations. Biodistribution studies and PET/CT imaging indicated favorable brain uptake: 0.54% ID/g and 0.59% ID/g at 2 minutes in normal and AD rats, respectively. Computational studies indicated that DTPA[Ch-DE]2 binds specifically to the Aβ fibrils while maintaining the receptor’s architectural integrity. In vivo studies show that [68Ga] Ga-DTPA[Ch-DE]2 has good brain uptake and retention in AD rats compared with normal.
Conclusion:: Thus, results suggest that [68Ga]Ga-DTPA[Ch-DE]2 could be a promising radiotracer for Aβ targeting and early diagnosis of AD.
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BibTeX
@article{ghiamaty2026design,
title = {{Design and Evaluation of a Chalcone-Based Dimeric Scaffold Targeting Amyloid-Beta Plaques for Early Detection of Alzheimer’s Disease: Synthesis, Radiolabeling, In Vivo Studies, and Integrated Molecular Docking and Dynamics Simulation}},
author = {Zahra Ghiamaty and Mehdi Akhlaghi and Safura Jokar and Hooman Hafezi and Omid Bavi and Mohammad Sharifzadeh and Omid Sabzevari and Mehdi Shafiee Ardestani and Tahereh Ghorbandaeipour and Mahboobeh Asadi and Mahshid Kiani and Sara Roustaei and Fatemeh Ebrahimi and Davood Beiki},
journal = {Advanced Pharmaceutical Bulletin},
year = {2026},
month = may,
doi = {10.34172/apb.46659},
url = {https://doi.org/10.34172/apb.46659},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Design and Evaluation of a Chalcone-Based Dimeric Scaffold Targeting Amyloid-Beta Plaques for Early Detection of Alzheimer’s Disease: Synthesis, Radiolabeling, In Vivo Studies, and Integrated Molecular Docking and Dynamics Simulation
AU - Zahra Ghiamaty
AU - Mehdi Akhlaghi
AU - Safura Jokar
AU - Hooman Hafezi
AU - Omid Bavi
AU - Mohammad Sharifzadeh
AU - Omid Sabzevari
AU - Mehdi Shafiee Ardestani
AU - Tahereh Ghorbandaeipour
AU - Mahboobeh Asadi
AU - Mahshid Kiani
AU - Sara Roustaei
AU - Fatemeh Ebrahimi
AU - Davood Beiki
PY - 2026
DA - 2026/05/19
JO - Advanced Pharmaceutical Bulletin
DO - 10.34172/apb.46659
UR - https://doi.org/10.34172/apb.46659
AB - Purpose:: Amyloid-Beta (Aβ) plaque imaging can serve as a desirable tool for early detection of Alzheimer’s disease (AD). This study presents a new dimer of a chalcone-based scaffold, [68Ga]Ga-DTPA[Ch-DE]2, as a potential radiotracer for Aβ plaques imaging. Methods:: The synthesis of DTPA[Ch-DE]2 and its radiolabeling with gallium-68 were characterized using techniques such as 1H-NMR, mass spectrometry, HPLC, and instant thin-layer chromatography. Neurotoxicity of DTPA[Ch-DE]2 was evaluated using the MTT assay. The stability of radiotracer was tested in various buffer systems and human serum albumin (HSA). The binding affinity of the radiotracer to Aβ aggregations was evaluted on the brain sections from both normal and AD rat models. Positron emission tomography-computed tomography (PET/CT) of brain imaging and Thioflavin S staining characterized the AD model. Biodistribution studies and PET/CT scans were performed on normal and AD rats. Computational studies also were conducted. Results:: [68Ga]Ga-DTPA[Ch-DE]2 was synthesized with over 93% radiochemical purity. It showed high stability in various buffer systems and HSA after 2 hours. The binding assay revealed strong affinity to Aβ42 aggregations. Biodistribution studies and PET/CT imaging indicated favorable brain uptake: 0.54% ID/g and 0.59% ID/g at 2 minutes in normal and AD rats, respectively. Computational studies indicated that DTPA[Ch-DE]2 binds specifically to the Aβ fibrils while maintaining the receptor’s architectural integrity. In vivo studies show that [68Ga] Ga-DTPA[Ch-DE]2 has good brain uptake and retention in AD rats compared with normal. Conclusion:: Thus, results suggest that [68Ga]Ga-DTPA[Ch-DE]2 could be a promising radiotracer for Aβ targeting and early diagnosis of AD.
SN - 2228-5881
SN - 2251-7308
ER -