Novel brain PET imaging agents: Strategies for imaging neuroinflammation in Alzheimer’s disease and mild cognitive impairment

Abstract

Alzheimer’s disease (AD) is a devastating neurodegenerative disease with a concealed onset and continuous deterioration. Mild cognitive impairment (MCI) is the prodromal stage of AD. Molecule-based imaging with positron emission tomography (PET) is critical in tracking pathophysiological changes among AD and MCI patients. PET with novel targets is a promising approach for diagnostic imaging, particularly in AD patients. Our present review overviews the current status and applications of in vivo molecular imaging toward neuroinflammation. Although radiotracers can remarkably diagnose AD and MCI patients, a variety of limitations prevent the recommendation of a single technique. Recent studies examining neuroinflammation PET imaging suggest an alternative approach to evaluate disease progression. This review concludes that PET imaging towards neuroinflammation is considered a promising approach to deciphering the enigma of the pathophysiological process of AD and MCI.

Cell-free DNA-based liquid biopsies in neurology

“… 128 Imaging modalities, including MRI and PET, can be used to confirm Alzheimer’s disease pathogenesis and even to identify cases during the prodromal period. 129 Recent advancements in techniques that can identify presymptomatic disease and predict cognitive decline, including amyloid- and tau-based PET radiotracers, 130–132 are particularly important given that disease progression may begin decades prior to clinically noticeable symptoms. 133 Protein-based liquid biopsies of the CSF and blood have also demonstrated good diagnostic and prognostic performance by targeting molecules, such as amyloid-beta, tau, NfL and GFAP.…”

Second Near-Infrared Macrophage-Biomimetic Nanoprobes for Photoacoustic Imaging of Neuroinflammation

“…In terms of early clinical diagnoses, magnetic resonance imaging infers the presence of inflammation by indirect signs based on extracellular water accumulation, which leads to unspecific signal-induced misdiagnoses. Positron emission tomography can detect neuroinflammation at the molecular level and thus has the potential to obtain early information on inflammation, while its radioactive side effects are of significant concerns. , In previous studies of animals, fluorescence imaging was commonly used to visualize neuroinflammation. However, this method was limited by its shallow penetration depth, low resolution, and inability to acquire depth information about the inflammatory lesion. , In the early stage of local inflammation in the CNS, the activated resident glial cells release inflammatory cytokines, which attract leukocytes from the bloodstream and stimulate the vascular endothelium to overexpress specific selectins and adhesion molecules, ultimately resulting in the recruitment of monocytes and macrophages into local inflammatory areas within the CNS .…”

“…Positron emission tomography can detect neuroinflammation at the molecular level and thus has the potential to obtain early information on inflammation, while its radioactive side effects are of significant concerns. 12,13 In previous studies of animals, fluorescence imaging was commonly used to visualize neuroinflammation. However, this method was limited by its shallow penetration depth, low resolution, and inability to acquire depth information about the inflammatory lesion.…”

Radiolabeled imaging agents for Alzheimer's disease

“…and magnetic resonance imaging have enabled definitive and differential diagnosis in the MCI stage [4,5]. Molecular imaging, particularly nuclear medicine combined with molecular imaging agents, has been proposed as an effective tool for the early diagnosis of AD and the monitoring of disease progression in MCI subjects [4][5][6].…”