Amyloid β-Binding Bifunctional Chelators with Favorable Lipophilicity for 64Cu Positron Emission Tomography Imaging in Alzheimer's Disease

Yujue Wang, Truc T. Huynh, Hong Jun Cho, Yung Ching Wang, Buck E. Rogers, Liviu M. Mirica

Research output: Contribution to journalArticlepeer-review

Abstract

Herein, we report a new series of bifunctional chelators (BFCs) with a high affinity for amyloid aggregates, a strong binding affinity toward Cu(II), and favorable lipophilicity for potential blood-brain barrier penetration. The alkyl carboxylate ester pendant arms offer up to 3 orders of magnitude higher binding affinity toward Cu(II) and enable the BFCs to form stable 64Cu-radiolabeled complexes. Among the five compounds tested, the 64Cu-YW-7 and 64Cu-YW-10 complexes exhibit strong and specific staining of amyloid plaques in ex vivo autoradiography studies. Importantly, these BFCs have promising partition coefficient (log Doct) values of 0.91-1.26 and show some brain uptake in biodistribution studies using CD-1 mice. Overall, these BFCs could serve as lead compounds for the development of positron emission tomography imaging agents for AD diagnosis.

Original languageEnglish (US)
Pages (from-to)12610-12620
Number of pages11
JournalInorganic Chemistry
Volume60
Issue number16
DOIs
StatePublished - Aug 16 2021

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Inorganic Chemistry

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