Divalent 2-(4-Hydroxyphenyl)benzothiazole Bifunctional Chelators for 64 Cu Positron Emission Tomography Imaging in Alzheimer's Disease.
Karna TerpstraYujue WangTruc T HuynhNilantha BandaraHong-Jun ChoBuck E RogersLiviu M MiricaPublished in: Inorganic chemistry (2022)
Herein, we report a new series of divalent 2-(4-hydroxyphenyl)benzothiazole bifunctional chelators (BFCs) with high affinity for amyloid β aggregates and favorable lipophilicity for blood-brain barrier penetration. The addition of an alkyl carboxylate ester pendant arm offers high binding affinity toward Cu(II). The novel BFCs form stable 64 Cu-radiolabeled complexes and exhibit promising partition coefficient (log D ) values of 1.05-1.85. Among the five compounds tested, the 64 Cu-YW-15 complex exhibits significant staining of amyloid β plaques in ex vivo autoradiography studies. In addition, biodistribution studies show that 64 Cu-YW-15-Me exhibits moderate brain uptake (0.69 ± 0.08 %ID/g) in wild type mice.
Keyphrases
- blood brain barrier
- positron emission tomography
- metal organic framework
- wild type
- computed tomography
- aqueous solution
- pet imaging
- high resolution
- white matter
- type diabetes
- cognitive decline
- multiple sclerosis
- high intensity
- magnetic resonance
- adipose tissue
- mass spectrometry
- skeletal muscle
- brain injury
- capillary electrophoresis