A Modest Increase in 11C-PK11195-Positron Emission Tomography TSPO Binding in Depression Is Not Associated With Serum C-Reactive Protein or Body Mass Index

Manavaki, Roido; Nettis, Maria Antonietta; Pariante, Carmine M.; Wlazly, Dominika; Dickinson, Amber; Foster, Andy; Knight, Clare; Leckey, Claire; Morgan, Paul T.; Morgan, Angharad R.; O’Hagan, Caroline; Touchard, Samuel; Khan, Shahid A.; Murphy, Phil; Parker, Christine A.; Patel, Jitandrakumar R.; Richardson, Jill C.; Acton, Paul D.; Austin, Nigel; Bhattacharya, Anindya; Carruthers, Nick; Boer, P. de; Drevets, Wayne C.; Isaac, John; Jones, Declan N.C.; Kemp, John A.; Kolb, Hartmuth C.; Nye, Jeff; Wittenberg, Gayle M.; Barker, Gareth; Bogdanova, Anna; Byrom, Heidi; Cash, Diana; Cattaneo, Annamaria; Enache, Daniela; Gee, Tony; Hastings, Caitlin; Kose, Melisa; Lombardo, Giulia; Mariani, Nicole; McLaughlin, Anna; Mondelli, Valeria; Nettis, Maria Antonietta; Nikkheslat, Naghmeh; Pariante, Carmine; Randall, Karen; Schubert, Julia; Sforzini, Luca; Sheridan, Hannah; Simmons, Camilla; Singh, Nisha; Turkheimer, Federico; Loo, Vicky Van; Veronese, Mattia; Rodriguez, Marta Vicente; Wood, Toby; Worrell, Courtney; Zajkowska, Zuzanna; Campbell, Brian; Egebjerg, Jan; Eriksson, Hans; Gastambide, François; Adams, Karen; Jeggo, Ross; Möeller, Thomas; Nelson, Bob; Plath, Niels; Thomsen, C.; Pederson, Jan; Zorn, Stevin H.; Deith, Catherine; Farmer, Scott; McClean, John A.; McPherson, Andrew; Penandes, Nagore; Scouller, Paul; Sutherland, Murray; Attenburrow, Mary-Jane; Benjamin, Jithen; Jones, Helen; Mada, Fran; Oladejo, Akintayo; Smith, Katy D.; Balice‐Gordon, Rita J.; Binneman, Brendon; Duerr, James M.; Fullerton, Terence; Goli, Veeru; Hughes, Zoe; Piro, Justin R.; Samad, Tarek A.; Sporn, Jonathan; Hoskins, Liz; Kohn, Charmaine; Wilcock, Lauren; Aigbirhio, Franklin I.; Bhatti, Junaid; Bullmore, Edward T.; Chamberlain, Sam; Correia, Marta; Crofts, Anna; Fryer, Tim D.; Graves, Martin J.; Hatton, Alex; Kitzbichler, Manfred G.; Lynall, Mary-Ellen; Maurice, Christina; O’Donnell, Ciara; Pointon, Linda; Hyslop, Peter St. George; Turner, Lorinda; Vértes, Petra E.; Widmer, Barry; Williams, Guy; Cavanagh, Jonathan; McColl, Alison; Shaw, Robin; Boddeke, Erik; Baird, Alison E.; Clare, Stuart; Cowen, P J; Huang, I-Shu; Hurley, Sam; Lovestone, Simon; Nevado‐Holgado, Alejo J.; Ribé, Elena M.; Vyas, Anviti; Winchester, Laura; Cleal, Madeleine; Gómez-Nicola, Diego; Mancuso, Renzo; Perry, Hugh; Cercignani, Mara; Clarke, Charlotte; Colasanti, Alessandro; Harrison, Neil A.; Murray, Rosemary; O’Connor, Jason C.; Mount, Howard T.J.

doi:10.1016/j.bpsc.2020.12.017

Cited by 11 publications

(19 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Though [ 18 F]FEPPA was successfully used in several large studies, the only study performed with (R)-[ 11 C]PK11195 (along with a pilot report [121]) revealed the same results in the anterior cingulate cortex (with a relatively high effect size), whereas the effects were less pronounced in the frontal cortex and the insula [122]. Importantly, these conclusions have been very recently confirmed in a new, large cohort of 51 patients scanned with (R)-[ 11 C] PK11195 [123,133].…”

Section: Depressionmentioning

confidence: 71%

Have (R)-[11C]PK11195 challengers fulfilled the promise? A scoping review of clinical TSPO PET studies

Chauveau

Becker

Boutin

2021

Eur J Nucl Med Mol Imaging

View full text Add to dashboard Cite

Purpose The prototypical TSPO radiotracer (R)-[11C]PK11195 has been used in humans for more than thirty years to visualize neuroinflammation in several pathologies. Alternative radiotracers have been developed to improve signal-to-noise ratio and started to be tested clinically in 2008. Here we examined the scientific value of these “(R)-[11C]PK11195 challengers” in clinical research to determine if they could supersede (R)-[11C]PK11195. Methods A systematic MEDLINE (PubMed) search was performed (up to end of year 2020) to extract publications reporting TSPO PET in patients with identified pathologies, excluding studies in healthy subjects and methodological studies. Results Of the 288 publications selected, 152 used 13 challengers, and 142 used (R)-[11C]PK11195. Over the last 20 years, the number of (R)-[11C]PK11195 studies remained stable (6 ± 3 per year), but was surpassed by the total number of challenger studies for the last 6 years. In total, 3914 patients underwent a TSPO PET scan, and 47% (1851 patients) received (R)-[11C]PK11195. The 2 main challengers were [11C]PBR28 (24%—938 patients) and [18F]FEPPA (11%—429 patients). Only one-in-ten patients (11%—447) underwent 2 TSPO scans, among whom 40 (1%) were scanned with 2 different TSPO radiotracers. Conclusions Generally, challengers confirmed disease-specific initial (R)-[11C]PK11195 findings. However, while their better signal-to-noise ratio seems particularly useful in diseases with moderate and widespread neuroinflammation, most challengers present an allelic-dependent (Ala147Thr polymorphism) TSPO binding and genetic stratification is hindering their clinical implementation. As new challengers, insensitive to TSPO human polymorphism, are about to enter clinical evaluation, we propose this systematic review to be regularly updated (living review).

show abstract

Section: Depressionmentioning

confidence: 71%

Have (R)-[11C]PK11195 challengers fulfilled the promise? A scoping review of clinical TSPO PET studies

Chauveau

Becker

Boutin

2021

Eur J Nucl Med Mol Imaging

View full text Add to dashboard Cite

show abstract

“…Despite these caveats, some studies using TSPO have also examined peripheral markers of inflammation, which may shed light on neuroimmune crosstalk. Here, the literature is again mixed, with many studies showing that TSPO binding is generally not strongly correlated with peripheral cytokines and acute phase reactants, 22–24 even when TSPO binding is increased in patients, 22 whereas others show significant positive or negative associations 19 . Using the TSPO radiotracer 11 C-DPA713, Coughlin and colleagues 24 examined patients in early-phase SZ and failed to find a significant relationship between TSPO and peripheral cytokines (IL-6, IFN γ , TNF α , IL-10), though they observed a significant positive association between IL-6 in the CSF and blood.…”

Section: Neuroimmune Crosstalk: Insights From Translator Protein Pet ...mentioning

confidence: 99%

The Effects of Peripheral Inflammation on the Brain—A Neuroimaging Perspective

Millett

Burdick

Kubicki

2022

Harv Rev Psychiatry

View full text Add to dashboard Cite

In the field of neuropsychiatry, neuroinflammation is one of the prevailing hypotheses to explain the pathophysiology of mood and psychotic disorders. Neuroinflammation encompasses an ill-defined set of pathophysiological processes in the central nervous system that cause neuronal or glial atrophy or death and disruptions in neurotransmitter signaling, resulting in cognitive and behavioral changes. Positron emission tomography for the brain-based translocator protein has been shown to be a useful tool to measure glial activation in neuropsychiatric disorders. Recent neuroimaging studies also indicate a potential disruption in the choroid plexus and blood-brain barrier, which modulate the transfer of ions, molecules, toxins, and cells from the periphery into the brain. Simultaneously, peripheral inflammatory markers have consistently been shown to be altered in mood and psychotic disorders. The crosstalk (i.e., the communication between peripheral and central inflammatory pathways) is not well understood in these disorders, however, and neuroimaging studies hold promise to shed light on this complex process. In the current Perspectives article, we discuss the neuroimaging insights into neuroimmune crosstalk offered in selected works. Overall, evidence exists for peripheral immune cell infiltration into the central nervous system in some patients, but the reason for this is unknown. Future neuroimaging studies should aim to extend our knowledge of this system and the role it likely plays in symptom onset and recurrence.

show abstract

“…30 Notably, in MDD, increased TSPO expression has been reported within brain regions involved in mood regulation, including the anterior cingulate cortex (ACC), prefrontal cortex (PFC), and insula. 7,9…”

Section: Introductionmentioning

confidence: 99%

Extra-axial inflammatory signal and its relation to peripheral and central immunity in depression

Eiff,

Bullmore,

Clatworthy

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

Although both central and peripheral inflammation have been consistently observed in depression, the relationship between the two remains obscure. Extra-axial immune cells may play a role in mediating the connection between central and peripheral immunity. This study investigates the potential roles of calvarial bone marrow and parameningeal spaces in mediating interactions between central and peripheral immunity in depression. Positron emission tomography was employed to measure regional TSPO expression in the skull and parameninges as a marker of inflammatory activity. This measure was correlated with brain TSPO expression and peripheral cytokine concentrations in a cohort enriched for heightened peripheral and central immunity comprising 51 individuals with depression and 25 healthy controls. The findings reveal a complex relationship between regional skull TSPO expression and both peripheral and central immunity. Facial and parietal skull bone TSPO expression showed significant associations with both peripheral and central immunity. TSPO expression in the confluence of sinuses was also linked to both central and peripheral immune markers. Group dependant elevations in TSPO expression within the occipital skull bone marrow were also found to be significantly associated with central inflammation. Significant associations between immune activity within the skull, parameninges, parenchyma, and periphery highlight the role of the skull bone marrow and venous sinuses as pivotal sites for peripheral and central immune interactions.

show abstract

A Modest Increase in 11C-PK11195-Positron Emission Tomography TSPO Binding in Depression Is Not Associated With Serum C-Reactive Protein or Body Mass Index

Cited by 11 publications

References 68 publications

Have (R)-[11C]PK11195 challengers fulfilled the promise? A scoping review of clinical TSPO PET studies

Have (R)-[11C]PK11195 challengers fulfilled the promise? A scoping review of clinical TSPO PET studies

The Effects of Peripheral Inflammation on the Brain—A Neuroimaging Perspective

Extra-axial inflammatory signal and its relation to peripheral and central immunity in depression

Contact Info

Product

Resources

About