Positron emission tomography (PET), which uses positron-emitting radionuclides to visualize and measure processes in the human body, is a useful noninvasive diagnostic tool for Alzheimer's disease (AD). The development of longer-lived radiolabeled compounds is essential for further expansion of the use of PET imaging in healthcare, and diagnostic agents employing longer-lived radionuclides such as 64Cu (t1/2 = 12.7 h, β+ = 17%, β- = 39%, electron capture EC = 43%, and Emax = 0.656 MeV) can accomplish this task. One limitation of 64Cu PET agents for neuroimaging applications is their limited lipophilicity due to the presence of several anionic groups needed to ensure strong Cu chelation. Herein, we evaluate a series of neutral chelators containing the 1,4,7-triazacyclononane or 2,11-diaza[3.3](2,6)pyridinophane macrocycles that have pyridyl-containing arms incorporating Aβ-peptide-interacting fragments. The crystal structures of the corresponding Cu complexes confirm that the pyridyl N atoms are involved in binding to Cu. Radiolabeling and autoradiography studies show that the compounds efficiently chelate 64Cu, and the resulting complexes exhibit specific binding to the amyloid plaques in the AD mouse brain sections versus wild-type controls.