TY - JOUR
T1 - Coordination Chemistry of Bifunctional Chemical Agents Designed for Applications in 64Cu PET Imaging for Alzheimer's Disease
AU - Sharma, Anuj K.
AU - Schultz, Jason W.
AU - Prior, John T.
AU - Rath, Nigam P.
AU - Mirica, Liviu M.
N1 - Funding Information:
We acknowledge research funding from the NIH (Grant R01GM114588), Alzheimer’s Association (Grant NIRG 12-259199), Washington University Alzheimer’s Disease Research Center (Grant NIH P50-AG05681), and McDonnell Center for Cellular and Molecular Neurobiology at Washington University School of Medicine.
Publisher Copyright:
© 2017 American Chemical Society.
PY - 2017/11/20
Y1 - 2017/11/20
N2 - Positron emission tomography (PET) is emerging as one of the most important diagnostic tools for brain imaging, yet the most commonly used radioisotopes in PET imaging, 11C and 18F, have short half-lives, and their usage is thus somewhat limited. By comparison, the 64Cu radionuclide has a half-life of 12.7 h, which is ideal for administering and imaging purposes. In spite of appreciable research efforts, high-affinity copper chelators suitable for brain imaging applications are still lacking. Herein, we present the synthesis and characterization of a series of bifunctional compounds (BFCs) based on macrocyclic 1,4,7-triazacyclononane and 2,11-diaza[3.3](2,6)pyridinophane ligand frameworks that exhibit a high affinity for Cu2+ ions. In addition, these BFCs contain a 2-phenylbenzothiazole fragment that is known to interact tightly with amyloid β fibrillar aggregates. Determination of the protonation constants (pKa values) and stability constants (log β values) of these BFCs, as well as characterization of the isolated copper complexes using X-ray crystallography, electron paramagnetic resonance spectroscopy, and electrochemical studies, suggests that these BFCs exhibit desirable properties for the development of novel 64Cu PET imaging agents for Alzheimer's disease.
AB - Positron emission tomography (PET) is emerging as one of the most important diagnostic tools for brain imaging, yet the most commonly used radioisotopes in PET imaging, 11C and 18F, have short half-lives, and their usage is thus somewhat limited. By comparison, the 64Cu radionuclide has a half-life of 12.7 h, which is ideal for administering and imaging purposes. In spite of appreciable research efforts, high-affinity copper chelators suitable for brain imaging applications are still lacking. Herein, we present the synthesis and characterization of a series of bifunctional compounds (BFCs) based on macrocyclic 1,4,7-triazacyclononane and 2,11-diaza[3.3](2,6)pyridinophane ligand frameworks that exhibit a high affinity for Cu2+ ions. In addition, these BFCs contain a 2-phenylbenzothiazole fragment that is known to interact tightly with amyloid β fibrillar aggregates. Determination of the protonation constants (pKa values) and stability constants (log β values) of these BFCs, as well as characterization of the isolated copper complexes using X-ray crystallography, electron paramagnetic resonance spectroscopy, and electrochemical studies, suggests that these BFCs exhibit desirable properties for the development of novel 64Cu PET imaging agents for Alzheimer's disease.
UR - http://www.scopus.com/inward/record.url?scp=85034582947&partnerID=8YFLogxK
U2 - 10.1021/acs.inorgchem.7b01883
DO - 10.1021/acs.inorgchem.7b01883
M3 - Article
C2 - 29112419
AN - SCOPUS:85034582947
SN - 0020-1669
VL - 56
SP - 13801
EP - 13814
JO - Inorganic Chemistry
JF - Inorganic Chemistry
IS - 22
ER -