Peripheral inflammation is associated with reduced influx of TSPO PET tracers into the brain: insights from a non-invasive mapping methodology

Barzon, Leonardo, Maccioni, Lucia, Moretto, Manuela, Giacomel, Alessio, Schubert, Julia J., Cousins, Oliver, Rosenzweig, Ivana, Mizuno, Yuya, Reis Marques, Tiago, Harrison, Neil A. ORCID: https://orcid.org/0000-0002-9584-3769, Fryer, Tim, Bullmore, Edward T., Mondelli, Valeria, Pariante, Carmine, Howes, Oliver, Turkheimer, Federico E. and Veronese, Mattia 2026. Peripheral inflammation is associated with reduced influx of TSPO PET tracers into the brain: insights from a non-invasive mapping methodology. Brain, Behavior, and Immunity 136 , 106779. 10.1016/j.bbi.2026.106779

PDF - Published Version Available under License Creative Commons Attribution. Download (8MB)

Abstract

Neuroinflammation is a hallmark of various brain disorders, including neuropsychiatric conditions like major depressive disorder and schizophrenia. Increasing evidence suggests that both peripheral and central inflammation play a critical role in central nervous system dysfunction associated with such disorders. There is evidence, particularly in preclinical models, of a mediating role of the blood–brain barrier in the relationship between peripheral and central immunity. However, this relationship is poorly studied in human cohorts and, importantly, little is known about its effect on the quantification of radioligands used to monitor neuroinflammation in vivo. To address this gap, a recently developed non-invasive method for estimating the blood-to-brain influx rate constant (K1) (Maccioni et al., 2024) was applied to TSPO PET imaging, a putative marker of neuroinflammation. In total, 358 dynamic TSPO PET scans from three different radiotracers ([11C]-PK11195, [18F]-DPA714, and [11C]-PBR28) were reanalyzed using data from healthy controls, as well as patients with depression and schizophrenia. The relationship between brain-wide K1 estimates, peripheral inflammatory marker C-reactive protein (CRP), sex, anthropometric measures, and disease states was systematically evaluated. A brain-wide negative correlation between peripheral inflammation and K1 was observed (range: [-0.33, −0.25]). Notably, this association was not influenced by diagnostic labels. Additionally, significant effects of body weight (or body mass index) and sex on K1 were identified. The findings were consistent at both regional and voxel levels, as well as across the three radiotracers. Imaging transcriptomics analyses revealed that the effect of CRP on K1 was associated with the expression of genes involved in transport and homeostasis. The study confirms that increased peripheral inflammation is associated with reduced blood-to-brain transport of TSPO tracers, suggesting a role for blood–brain barrier permeability in the observed effect. This finding supports the emerging model of peripheral-to-central immune interactions via brain barriers by Turkheimer and colleagues (2023). By considering variables such as body mass, sex, and peripheral inflammatory status, this research provides crucial insights into the use of TSPO PET in psychiatry and the interpretability of its findings.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Medicine
Publisher:	Elsevier
ISSN:	0889-1591
Date of First Compliant Deposit:	6 May 2026
Date of Acceptance:	22 April 2026
Last Modified:	06 May 2026 15:30
URI:	https://orca.cardiff.ac.uk/id/eprint/186833

Actions (repository staff only)

Edit Item