K Collste1, A Forsberg2, A Varrone2, N Amini2, S Aeinehband3, I Yakushev2,4, C Halldin2, L Farde2, S Cervenka2. 1. Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden. karin.collste@ki.se. 2. Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden. 3. Department of Clinical Neuroscience, Neuroimmunology Unit, Karolinska Institutet, Stockholm, Sweden. 4. Department of Nuclear Medicine and TUM Neuroimaging Center (TUM-NIC), Technische Universität München, Munich, Germany.
Abstract
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.
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.
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