PT  - JOURNAL ARTICLE
AU  - Gjertrud L. Laurell
AU  - Pontus Plavén-Sigray
AU  - Aurelija Jucaite
AU  - Andrea Varrone
AU  - Kelly P. Cosgrove
AU  - Claus Svarer
AU  - Gitte M. Knudsen
AU  - Karolinska Schizophrenia Project Consortium
AU  - R. Todd Ogden
AU  - Francesca Zanderigo
AU  - Simon Cervenka
AU  - Ansel T. Hillmer
AU  - Martin Schain
TI  - Nondisplaceable Binding Is a Potential Confounding Factor in <sup>11</sup>C-PBR28 Translocator Protein PET Studies
AID  - 10.2967/jnumed.120.243717
DP  - 2021 Mar 01
TA  - Journal of Nuclear Medicine
PG  - 412--417
VI  - 62
IP  - 3
4099  - http://jnm.snmjournals.org/content/62/3/412.short
4100  - http://jnm.snmjournals.org/content/62/3/412.full
SO  - J Nucl Med2021 Mar 01; 62
AB  - 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 VT. Methods: 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 VND. Conclusion: Our findings suggest that in TSPO PET studies, nondisplaceable binding can differ between patient groups and conditions and should therefore be considered.