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. 2021 Mar;62(3):412-417.
doi: 10.2967/jnumed.120.243717. Epub 2020 Jul 17.

Nondisplaceable Binding Is a Potential Confounding Factor in 11C-PBR28 Translocator Protein PET Studies

Gjertrud L Laurell  1 , Pontus Plavén-Sigray  2   3 , Aurelija Jucaite  3   4 , Andrea Varrone  3 , Kelly P Cosgrove  5   6 , Claus Svarer  2 , Gitte M Knudsen  2   7 ; Karolinska Schizophrenia Project Consortium; R Todd Ogden  8   9 , Francesca Zanderigo  8   10 , Simon Cervenka  3 , Ansel T Hillmer  5   6   11 , Martin Schain  2
Affiliations

Nondisplaceable Binding Is a Potential Confounding Factor in 11C-PBR28 Translocator Protein PET Studies

Gjertrud L Laurell et al. J Nucl Med. 2021 Mar.

Abstract

The PET ligand 11C-PBR28 (N-((2-(methoxy-11C)-phenyl)methyl)-N-(6-phenoxy-3-pyridinyl)acetamide) binds to the 18-kDa translocator protein (TSPO), a biomarker of glia. In clinical studies of TSPO, the ligand total distribution volume, VT, is frequently the reported outcome measure. Since VT is the sum of the ligand-specific distribution volume (VS) and the nondisplaceable-binding distribution volume (VND), differences in VND across subjects and groups will have an impact on VTMethods: Here, we used a recently developed method for simultaneous estimation of VND (SIME) to disentangle contributions from VND and VS Data from 4 previously published 11C-PBR28 PET studies were included: before and after a lipopolysaccharide challenge (8 subjects), in alcohol use disorder (14 patients, 15 controls), in first-episode psychosis (16 patients, 16 controls), and in Parkinson disease (16 patients, 16 controls). In each dataset, regional VT estimates were obtained with a standard 2-tissue-compartment model, and brain-wide VND was estimated with SIME. VS was then calculated as VT - VND VND and VS were then compared across groups, within each dataset. Results: A lower VND was found for individuals with alcohol-use disorder (34%, P = 0.00084) and Parkinson disease (34%, P = 0.0032) than in their corresponding controls. We found no difference in VND between first-episode psychosis patients and their controls, and the administration of lipopolysaccharide did not change VNDConclusion: Our findings suggest that in TSPO PET studies, nondisplaceable binding can differ between patient groups and conditions and should therefore be considered.

Keywords: 11C-PBR28; PET; kinetic modeling; simultaneous estimation; translocator protein.

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Figures

None
Graphical abstract
FIGURE 1.
FIGURE 1.
Change in outcome measures (VT, VS, and VND) between pre- and postlipopolysaccharide scans in cerebellum (A) and frontal cortex (B). Individual subjects are connected with a line. P values and percentage difference (perc. diff.) between pre- and postlipopolysaccharide scans are shown. HAB = high-affinity binder; MAB = mixed-affinity binder.
FIGURE 2.
FIGURE 2.
(A and C) Difference in outcome measures (VT, VS, and VND) between controls (Ctrl) and subjects with AUD in cerebellum (A) and frontal cortex (C). (B) Zoomed view of results for VND. P values and percentage difference (perc. diff.) between controls and patients are shown. HAB = high-affinity binder; MAB = mixed-affinity binder.
FIGURE 3.
FIGURE 3.
(A and C) Difference in outcome measures (VT, VS, and VND) between controls (Ctrl) and FEP patients in cerebellum (A) and frontal cortex (C). (B) Zoomed view of results for VND. P values and percentage difference (perc. diff.) between controls and patients are shown. HAB = high-affinity binder; MAB = mixed-affinity binder.
FIGURE 4.
FIGURE 4.
(A and C) Difference in outcome measures (VT, VS, and VND) between controls (Ctrl) and PD patients in cerebellum (A) and striatum (C). (B) Zoomed view of results for VND. P values and percentage difference (perc. diff.) between controls and patients are shown. HAB = high-affinity binder; MAB = mixed-affinity binder.
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