title: Positron Emission Tomography studies with [11C]PBR28 in the Healthy Rodent Brain: Validating SUV as an Outcome Measure of Neuroinflammation.
abstract: Molecular imaging of the 18 kD Translocator protein (TSPO) with positron emission tomography (PET) is of great value for studying neuroinflammation in rodents longitudinally. Quantification of the TSPO in rodents is, however, quite challenging. There is no suitable reference region and the use of plasma-derived input is not an option for longitudinal studies. The aim of this study was therefore to evaluate the use of the standardized uptake value (SUV) as an outcome measure for TSPO imaging in rodent brain PET studies, using [11C]PBR28. In the first part of the study, healthy male Wistar rats (n = 4) were used to determine the correlation between the distribution volume (VT, calculated with Logan graphical analysis) and the SUV. In the second part, healthy male Wistar rats (n = 4) and healthy male C57BL/6J mice (n = 4), were used to determine the test-retest variability of the SUV, with a 7-day interval between measurements. Dynamic PET scans of 63 minutes were acquired with a nanoScan PET/MRI and nanoScan PET/CT. An MRI scan was made for anatomical reference with each measurement. The whole brain VT of [11C]PBR28 in rats was 42.9 ± 1.7. A statistically significant correlation (r2 = 0.96; p < 0.01) was found between the VT and the SUV. The test-retest variability in 8 brain region ranged from 8 to 20% in rats and from 7 to 23% in mice. The interclass correlation coefficient (ICC) was acceptable to excellent for rats, but poor to acceptable for mice.
  
  
  CONCLUSIONS
  The SUV of [11C]PBR28 showed a high correlation with VT as well as good test-retest variability. For future longitudinal small animal PET studies the SUV can thus be used to describe [11C]PBR28 uptake in healthy brain tissue. Based on the present observations, further studies are needed to explore the applicability of this approach in small animal disease models, with special regard to neuroinflammatory models.
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Centrum for Psychiatry Research, Stockholm, Sweden.
authors.forename: Miklós
authors.initials: M
authors.lastname: Tóth
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Centrum for Psychiatry Research, Stockholm, Sweden; Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Janine
authors.initials: J
authors.lastname: Doorduin
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Centrum for Psychiatry Research, Stockholm, Sweden.
authors.forename: Jenny
authors.initials: J
authors.lastname: Häggkvist
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Centrum for Psychiatry Research, Stockholm, Sweden.
authors.forename: Andrea
authors.initials: A
authors.lastname: Varrone
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Centrum for Psychiatry Research, Stockholm, Sweden.
authors.forename: Nahid
authors.initials: N
authors.lastname: Amini
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Centrum for Psychiatry Research, Stockholm, Sweden; Imperial College-NTU, Lee Chian Kong School of Medicine, Nanyang Technological University, Singapore.
authors.forename: Christer
authors.initials: C
authors.lastname: Halldin
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Centrum for Psychiatry Research, Stockholm, Sweden; Imperial College-NTU, Lee Chian Kong School of Medicine, Nanyang Technological University, Singapore.
authors.forename: Balázs
authors.initials: B
authors.lastname: Gulyás
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002352:Carrier Proteins / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D051379:Mice; D057054:Molecular Imaging / Q000379:methods*; D049268:Positron-Emission Tomography; D051381:Rats; D018079:Receptors, GABA / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000378:metabolism*; D015203:Reproducibility of Results
chemical_list: C463819:Bzrp protein, mouse; D002250:Carbon Radioisotopes; D002352:Carrier Proteins; D018079:Receptors, GABA; D011963:Receptors, GABA-A; C069997:Tspo protein, rat