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 Publisher



Ghiamaty Z ; Akhlaghi M ; Jokar S ; Hafezi H ; Bavi O ; Sharifzadeh M ; Sabzevari O ; Ardestani M S ; Ghorbandaeipour T ; Asadi M ; Kiani M ; Roustaei S ; Ebrahimi F ; Beiki D
Source: Advanced Pharmaceutical Bulletin Published:2026

Abstract

Introduction: 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. © 2026 The Author (s).