Positron emission tomography (PET) is a non-invasive imaging technology that can reveal molecular alterations in the brains of Alzheimer's disease (AD) patients with high sensitivity and specificity, which is crucial for clinical diagnosis, disease staging, and monitoring potential therapeutic approaches. Several biomarkers contribute to the clinical diagnosis of AD, and according to the evolving ATX(N) framework, these biomarkers can be classified into the amyloid-β (A) pathway, Tau-mediated pathophysiology (T), neurodegeneration (N), and other related molecular and cellular network changes in the AD continuum (X), such as neuroinflammation, synaptic dysfunction, and neurochemical deficits. This review provides an overview of PET tracers reported for several typical and classical targets in early AD diagnosis and compares tracers targeting the same biomarkers. We believe this review will support and facilitate progress in early AD diagnosis and further propose the future potential of both PET tracers and targets. 

Current status of PET tracers for the early diagnosis of Alzheimer's disease

Sv2a pet在神经退行性疾病中的应用

Dysfunction or decreased expression of synaptic vesicle glycoprotein 2A (SV2A) is closely related to the progression of neurodegenerative diseases and psychiatric disorders. The development of positron emission tomography (PET) tracers targeting SV2A can provide a strong imaging basis for the diagnosis and treatment of these diseases. Herein we report the synthesis of the novel radiotracer [18F]BIBD-181 and its preclinical evaluation. The absolute configuration of BIBD-181 was confirmed by the single-crystal structure of its precursor. The in vitro binding assay of BIBD-181 showed high SV2A binding affinity. Compared with previously reported tracers, [18F]BIBD-181 has mild labeling conditions, simple operation, and high yield. The in vivo metabolism of [18F]BIBD-181 is similar to that of UCB derivatives, and the metabolites do not interfere with brain PET imaging. Biodistribution and PET studies showed that [18F]BIBD-181 has high brain uptake and good pharmacokinetics. Autoradiography and PET inhibition studies indicated that [18F]BIBD-181 specifically binds SV2A. Because [18F]BIBD-181 exhibits excellent properties, it may be a reliable probe of quantities for SV2A-related disease diagnosis.

[18F]BIBD-181: A Novel Positron Emission Tomography Tracer Specific for Synaptic Vesicle Glycoprotein 2A.

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[18F]BIBD-181: A Novel Positron Emission Tomography Tracer Specific for Synaptic Vesicle Glycoprotein 2A.