Test–retest reproducibility of [11C]PBR28 binding to TSPO in healthy control subjects

• Published in: European journal of nuclear medicine and molecular imaging Vol. 43; no. 1; pp. 173 - 183
• Main Authors: Collste, K., Forsberg, A., Varrone, A., Amini, N., Aeinehband, S., Yakushev, I., Halldin, C., Farde, L., Cervenka, S.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.01.2016; Springer Nature B.V
• Subjects: Brain; Brain imaging; C-11; Carbon Radioisotopes; Cardiology; Female; Genotype; Healthy Volunteers; Humans; Imaging; Male; Medical imaging; Medicine; Medicine & Public Health; Nuclear Medicine; Oncology; Original Article; Orthopedics; PBR28; PET; Protein Binding; Proteins; Pyrimidines - metabolism; Radiology; Receptors, GABA - genetics; Receptors, GABA - metabolism; Reproducibility of Results; Test-retest; Young Adult; PBR28; Test–retest; C; Brain imaging; PET; 11C
• ISSN: 1619-7070; 1619-7089; 1619-7089
• DOI: 10.1007/s00259-015-3149-8

Purpose The PET radioligand [ 11 C]PBR28 binds to the translocator protein (TSPO), a marker of brain immune activation. We examined the reproducibility of [ 11 C]PBR28 binding in healthy subjects with quantification on a regional and voxel-by-voxel basis. In addition, we performed a preliminary analysis of diurnal changes in TSPO availability. Methods Twelve subjects were examined using a high-resolution research tomograph and [ 11 C]PBR28, six in the morning and afternoon of the same day, and six in the morning on two separate days. Regional volumes of distribution ( V T ) were derived using a region-of-interest based two-tissue compartmental analysis (2TCM), as well as a parametric approach. Metabolite-corrected arterial plasma was used as input function. Results For the whole sample, the mean absolute variability in V T in the grey matter (GM) was 18.3 ± 12.7 %. Intraclass correlation coefficients in GM regions ranged from 0.90 to 0.94. Reducing the time of analysis from 91 to 63 min yielded a variability of 16.9 ± 14.9 %. There was a strong correlation between the parametric and 2TCM-derived GM values ( r  = 0.99). A significant increase in GM V T was observed between the morning and afternoon examinations when using secondary methods of quantification ( p  = 0.028). In the subjects examined at the same time of the day, the absolute variability was 15.9 ± 12.2 % for the 91-min 2TCM data. Conclusion V T of [ 11 C]PBR28 binding showed medium reproducibility and high reliability in GM regions. Our findings support the use of parametric approaches for determining [ 11 C]PBR28 V T values, and indicate that the acquisition time could be shortened. Diurnal changes in TSPO binding in the brain may be a potential confounder in clinical studies and should be investigated further.