Molecular Design of Magnetic Resonance Imaging Agents Binding to Amyloid Deposits

Abstract

The ability to detect and monitor amyloid deposition in the brain using non-invasive imaging techniques provides valuable insights into the early diagnosis and progression of Alzheimer’s disease and helps to evaluate the efficacy of potential treatments. Magnetic resonance imaging (MRI) is a widely available technique offering high-spatial-resolution imaging. It can be used to visualize amyloid deposits with the help of amyloid-binding diagnostic agents injected into the body. In recent years, a number of amyloid-targeted MRI probes have been developed, but none of them has entered clinical practice. We review the advances in the field and deduce the requirements for the molecular structure and properties of a diagnostic probe candidate. These requirements make up the base for the rational design of MRI-active small molecules targeting amyloid deposits. Particular attention is paid to the novel cryo-EM structures of the fibril aggregates and their complexes, with known binders offering the possibility to use computational structure-based design methods. With continued research and development, MRI probes may revolutionize the diagnosis and treatment of neurodegenerative diseases, ultimately improving the lives of millions of people worldwide.

Development of Triphenylmethane Dyes for In Vivo Fluorescence Imaging of Aβ Oligomers

“…For the noninvasive detection of targets in the brain, molecular imaging such as nuclear medicine imaging 16 (positron emission tomography: PET, and single-photon emission computed tomography: SPECT), magnetic resonance imaging (MRI), 17 and fluorescence imaging 18 have been used. Radiation-based PET and SPECT can detect targets located in deep tissue with high sensitivity but are time-consuming and costly due to facility and equipment limitations, with the risk of radiation exposure to both patients and technicians.…”

“…MRI involves no risk of radiation exposure, but its sensitivity is low. 17 Fluorescence imaging, on the other hand, does not expose the patient to radiation, is simple and inexpensive, and produces images with favorable contrast. 18 Thus, fluorescence imaging is valuable for the in vivo detection of Aβ oligomers.…”

“…Radiation-based PET and SPECT can detect targets located in deep tissue with high sensitivity but are time-consuming and costly due to facility and equipment limitations, with the risk of radiation exposure to both patients and technicians. MRI involves no risk of radiation exposure, but its sensitivity is low . Fluorescence imaging, on the other hand, does not expose the patient to radiation, is simple and inexpensive, and produces images with favorable contrast .…”

Alzheimer’s Disease Biomarker Detection Using Field Effect Transistor-Based Biosensor

“…Acetylcholine (Ach), a neurotransmitter, intimately connects to the neural signal transmission, and a deficiency of Ach concentration production induces AD progression [8]. To detect these AD biomarkers, a variety of methods has been employed, from conventional methods, such as positron emission tomography (PET) [16], magnetic Biosensors 2023, 13, 987 2 of 18 resonance imaging (MRI) [17], and near-infrared fluorescence (NIRF) [18], to modern methods, such as electrochemistry [19,20], fluorescence [21], and colorimetry [22,23]. Each of these provides a particular insight into AD and has advantages and disadvantages.…”

“…Each of these provides a particular insight into AD and has advantages and disadvantages. Conventional methods provide intuitive observation at low spatial resolution [16][17][18], and optical methods generally have trouble-free operation and visualization at a low limit of detection (LOD) [22][23][24]. A combination of optical methods effectively improves the LOD [25].…”