Amyloid β-Binding Bifunctional Chelators with Favorable Lipophilicity for 64Cu Positron Emission Tomography Imaging in Alzheimer's Disease.
Yujue WangTruc T HuynhHong-Jun ChoYung-Ching WangBuck E RogersLiviu M MiricaPublished in: Inorganic chemistry (2021)
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.
Keyphrases
- positron emission tomography
- computed tomography
- blood brain barrier
- metal organic framework
- aqueous solution
- pet imaging
- high resolution
- pet ct
- type diabetes
- cerebral ischemia
- binding protein
- risk assessment
- magnetic resonance imaging
- adipose tissue
- ionic liquid
- photodynamic therapy
- mild cognitive impairment
- human health
- magnetic resonance
- subarachnoid hemorrhage
- high fat diet induced
- case control
- insulin resistance
- fluorescence imaging