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Synthesis and evaluation of DAPH derivative as a potential imaging agent for β-amyloid plaques in the brain

¹ Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, China

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Objectives: To date, the main strategy for developing new imaging probes has focused on research into plaque-binding ThT and CR derivatives. So, design of radiotracers with novel core structures to image Aβ in vivo will be a challenge. 4,5-Dianilinophthalimide (DAPH), with its ability to inhibit and reverse β-sheet containing fibrils, is believed to bind the Aβ fibrils and plaques. This prompted us to apply it as a promising candidate of novel core structure for Aβ imaging agents. Here we report the synthesis and evaluation of DAPH derivative as a potential ligand for Aβ plaques.

Methods: Novel radioiodinated DAPH derivative of [I-125]-4-iodoanilinophthalimide was achieved by an iododestannylation reaction. The tributyltin derivative was prepared by tributyltin exchange reaction from its bromide precursor, which was obtained from phthalimide by N-methylation, nitration, reduction with stannous chloride, and coupling with 1-bromo-4-iodobenzene. HPLC-purified [I-125] ligand showed radiochemical purity >98% with a theoretical specific activity (~2000 Ci/mmol). Its binding to post mortem human AD brain homogenates was measured.

Results: [I-125] ligand displayed excellent binding affinity for human AD brain homogenates in vitro with Kd= 0.21±0.08nM.

Conclusions: This result demonstrates that DAPH derivative has high binding affinity for Aβ aggregates. Preparation and in vivo evaluation of [C-11]labelled DAPH derivatives are currently underway.

Research Support: 1. Funded by NSFC (20471011). 2. Thanks to Radiopharmeceutical Center, Institute of Applied Physics, Shanghai, China.

This Article Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Duan, X. Articles by Liu, B. PubMed Articles by Duan, X. Articles by Liu, B.