Divalent 2-(4-Hydroxyphenyl)benzothiazole Bifunctional Chelators for 64Cu Positron Emission Tomography Imaging in Alzheimer's Disease

Karna Terpstra; Yujue Wang; Truc T. Huynh; Nilantha Bandara; Hong Jun Cho; Buck E. Rogers; Liviu M. Mirica

doi:10.1021/acs.inorgchem.2c02740

Divalent 2-(4-Hydroxyphenyl)benzothiazole Bifunctional Chelators for ⁶⁴Cu Positron Emission Tomography Imaging in Alzheimer's Disease

Karna Terpstra, Yujue Wang, Truc T. Huynh, Nilantha Bandara, Hong Jun Cho, Buck E. Rogers, Liviu M. Mirica

Research output: Contribution to journal › Article › peer-review

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Abstract

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 ⁶⁴Cu-radiolabeled complexes and exhibit promising partition coefficient (logD) values of 1.05-1.85. Among the five compounds tested, the ⁶⁴Cu-YW-15 complex exhibits significant staining of amyloid β plaques in ex vivo autoradiography studies. In addition, biodistribution studies show that ⁶⁴Cu-YW-15-Me exhibits moderate brain uptake (0.69 ± 0.08 %ID/g) in wild type mice. copy; 2022 American Chemical Society.

Original language	English
Pages (from-to)	20326-20336
Number of pages	11
Journal	Inorganic Chemistry
Volume	61
Issue number	50
DOIs	https://doi.org/10.1021/acs.inorgchem.2c02740
State	Published - Dec 19 2022

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title = "Divalent 2-(4-Hydroxyphenyl)benzothiazole Bifunctional Chelators for 64Cu Positron Emission Tomography Imaging in Alzheimer's Disease",

abstract = "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 64Cu-radiolabeled complexes and exhibit promising partition coefficient (logD) values of 1.05-1.85. Among the five compounds tested, the 64Cu-YW-15 complex exhibits significant staining of amyloid β plaques in ex vivo autoradiography studies. In addition, biodistribution studies show that 64Cu-YW-15-Me exhibits moderate brain uptake (0.69 ± 0.08 %ID/g) in wild type mice. copy; 2022 American Chemical Society.",

author = "Karna Terpstra and Yujue Wang and Huynh, {Truc T.} and Nilantha Bandara and Cho, {Hong Jun} and Rogers, {Buck E.} and Mirica, {Liviu M.}",

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doi = "10.1021/acs.inorgchem.2c02740",

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T1 - Divalent 2-(4-Hydroxyphenyl)benzothiazole Bifunctional Chelators for 64Cu Positron Emission Tomography Imaging in Alzheimer's Disease

AU - Terpstra, Karna

AU - Wang, Yujue

AU - Huynh, Truc T.

AU - Bandara, Nilantha

AU - Cho, Hong Jun

AU - Rogers, Buck E.

AU - Mirica, Liviu M.

PY - 2022/12/19

Y1 - 2022/12/19

N2 - 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 64Cu-radiolabeled complexes and exhibit promising partition coefficient (logD) values of 1.05-1.85. Among the five compounds tested, the 64Cu-YW-15 complex exhibits significant staining of amyloid β plaques in ex vivo autoradiography studies. In addition, biodistribution studies show that 64Cu-YW-15-Me exhibits moderate brain uptake (0.69 ± 0.08 %ID/g) in wild type mice. copy; 2022 American Chemical Society.

AB - 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 64Cu-radiolabeled complexes and exhibit promising partition coefficient (logD) values of 1.05-1.85. Among the five compounds tested, the 64Cu-YW-15 complex exhibits significant staining of amyloid β plaques in ex vivo autoradiography studies. In addition, biodistribution studies show that 64Cu-YW-15-Me exhibits moderate brain uptake (0.69 ± 0.08 %ID/g) in wild type mice. copy; 2022 American Chemical Society.

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Divalent 2-(4-Hydroxyphenyl)benzothiazole Bifunctional Chelators for ⁶⁴Cu Positron Emission Tomography Imaging in Alzheimer's Disease

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