Association between FDG- and TSPO-PET signals across human and animal studies investigating neurodegenerative conditions: a systematic review.

Background: Fluorodeoxyglucose (FDG)-PET hypometabolism is considered a biomarker of neurodegeneration. However, recent evidence revealed that glial cells contribute to the FDG-PET signal. In this context, microglial changes have been evaluated with 18-kDa translocator protein (TSPO)-PET radiopharmaceuticals. While several studies have concomitantly conducted FDG- and TSPO-PET imaging, their associations remain controversial.

Objective: We systematically revised multi-tracer preclinical and clinical studies using FDG- and TSPO-PET to investigate neurodegenerative conditions.

Results: From 401 studies, 14 preclinical studies, 7 clinical studies and 1 study including both met the inclusion criteria. The preclinical studies included mouse models of amyloid, tau, and neurotoxins, whereas the clinical studies investigated Alzheimer's disease, Parkinson's disease and frontotemporal lobar degeneration. Most clinical studies found a negative association between FDG- and TSPO-PET signals, whereas animal studies showed mixed results being highly dependent on the radiotracer used.

Discussion: Our findings support the connection between glial and metabolic changes in the brain while highlighting glial heterogeneity between species and the specificities of TSPO-PET radiotracers. To better understand the dynamic associations between FDG- and TSPO-PET, it is essential to conduct longitudinal studies during the early stages of neurodegenerative disorders, along with the use of novel mouse models that more accurately represent these conditions.