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Glutamate is an important excitatory neurotransmitter, and vesicular glutamate transporters (VGLUTs) are critical in regulating the extent of glutamate release. Because initial increase and late stage decrease in VGLUT expression were implicated in progressive Alzheimer's disease (AD), VGLUTs can be a new imaging target for diagnosing AD. In this study, we have designed and synthesized a new multimodal gadolinium contrast agent conjugated with rose bengal to target VGLUTs (Gd-DO3A-RB). In addition to high kinetic and pH stability, magnetic resonance and fluorescence imaging using Gd-DO3A-RB showed high affinity to VGLUT1. Using the AD animal model (5XFAD), in vivo MRI with a Gd-DO3A-RB showed less MR signal enhancement in 5XFAD mouse brain than that of age-matched normal C57BL/6 mouse, suggesting a late stage decrease in VGLUT expression in AD animal model. Therefore, this new VGLUT targeting gadolinium contrast agent demonstrated a strong potential as a new diagnostic tool for AD with multimodal imaging capability. [ABSTRACT FROM AUTHOR]

Ultra-high-field (UHF) magnetic resonance imaging (MRI) can open up new avenues in clinical diagnostic imaging. Its sensitivity can be further improved using contrast agents (CAs). Therefore, developing low-molecular-weight MR CAs that are efficient under UHF is crucial to ensure taking full advantage of MR imaging at UHF. Moreover, designing highly stable UHF liver-specific CA has been challenging. Here, using dysprosium (Dy3+), which relaxes water protons via a Curie relaxation that increases T 2 relaxation substantially with the magnetic field strength, we report a new macrocyclic liver specific Dy3+ complex (Dy[DO3A-EOB]). We observed a 7.06 times higher r 2 / r 1 ratio of Dy[DO3A-EOB] at 9.4 T than that of 1.5 T, which suggests a superior negative-enhancing MR CA at UHF. In vivo MR imaging results further demonstrated that Dy[DO3A-EOB] showed a much strong negative enhancement at UHF (9.4 T) than under a low field (1.5 T). It was also found that, in addition to the ligand structure, the metal itself plays an important role in determining the liver uptake pattern of the CA. Therefore, we successfully demonstrated the first example of a small-molecular-weight liver-specific Dy3+ complex acting as a T 2 CA with high sensitivity at UHF for diagnosis of liver diseases. [ABSTRACT FROM AUTHOR]

Multifunctional imaging of the deposition of amyloid-beta (Aβ) aggregates in the brain is of great importance in diagnosing Alzheimer's disease. Herein, we report a multifunctional Aβ-targeting small-molecular-weight gadolinium (Gd)-based contrast agent (CA), Gd-DO3A-Chal (a new Gd-chelate conjugated with chalcone), that showed 8 times higher binding affinity to Aβ aggregates than a previously reported Gd-chelate conjugated with Pittsburgh compound B. Gd-DO3A-Chal showed multimodal imaging capability. As a new fluorescence imaging probe, Gd-DO3A-Chal showed a good match with immunostained images using 6E10 monoclonal antibodies for the detection of Aβ aggregates in 5XFAD transgenic mouse brain sections. For in vivo magnetic resonance (MR) imaging without blood-brain barrier disruption, longitudinal relaxation time (T 1)-weighted MR images after intravenous administration of Gd-DO3A-Chal showed signal enhancement of the Aβ distribution in living 5XFAD transgenic mouse brain. Therefore, in vivo MR images for Aβ detection in addition to fluorescent optical images of Aβ aggregates with high specificity and sensitivity using this new multifunctional Aβ-targeting CA were successfully demonstrated. [ABSTRACT FROM AUTHOR]