Design of a multivalent bifunctional chelator for diagnostic 64Cu PET imaging in Alzheimer’s disease

Hong-Jun Cho, Truc T. Huynh, Buck E. Rogers, Liviu M. Mirica

Research output: Contribution to journalArticlepeer-review

Abstract

Metal radiotracers exhibit beneficial properties that can improve in vivo positron emission tomography (PET) imaging over traditional radionuclides, such as longer half-lives, facile last-stage radiolabeling steps, and the potential for dual imaging-therapy applications. Among such radionuclides, 64Cu exhibits a longer half-life (t1/2 = 12.7 h) that allows for later PET imaging times and the ability to distribute 64Cu imaging agents to facilities that do not have an on-site cyclotron. Herein, we report a 64Cu PET imaging agent that shows appreciable in vivo brain uptake and exhibits high specific affinity for beta-amyloid aggregates, leading to the successful PET imaging of amyloid plaques in the brains of 5xFAD mice versus those of wild-type mice.Herein, we report a 64Cu positron emission tomography (PET) imaging agent that shows appreciable in vivo brain uptake and exhibits high specific affinity for beta-amyloid (Aβ) aggregates, leading to the successful PET imaging of amyloid plaques in the brains of 5xFAD mice versus those of wild-type mice. The employed approach uses a bifunctional chelator with two Aβ-interacting fragments that dramatically improves the Aβ-binding affinity and lipophilicity for favorable bloodtextendashbrain barrier penetration, while the use of optimized-length spacers between the Cu-chelating group and the Aβ-interacting fragments further improves the in vivo Aβ-binding specificity and brain uptake of the corresponding 64Cu PET imaging agent.
Original languageEnglish (US)
JournalProceedings of the National Academy of Sciences
DOIs
StatePublished - Nov 24 2020

Keywords

  • Alzheimer’s disease
  • multivalent effect
  • (Aβ) peptide
  • amyloid beta
  • blood–brain barrier
  • positron emission tomography imaging

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