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. In conclusion: 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.
Highlights
Activation of microglia has been implicated in the pathophysiology of many neurological and psychiatric diseases [1,2]
The present study have demonstrated that standardized uptake value (SUV) is a reliable outcome measure for [11C]PBR28 in rats
The SUV showed a high and statistical significant correlation with the volume of distribution (VT) obtained with 2-TCM and Logan analysis
Summary
Activation of microglia has been implicated in the pathophysiology of many neurological and psychiatric diseases [1,2]. In order to understand the role and nature of microglia activation in brain disease processes, studies in small animals are of major importance. Small animal positron emission tomography (PET) is of great value for studying microglia activation in disease models in rodents, especially because the technique allows for non-invasive assessment of longitudinal changes. The first radioligand that was widely used for imaging of microglia activation was [11C] PK11195 [6] This radioligand has numerous limitation [7], including a high level of non-specific binding and a poor signal-to-noise ratio. [11C]PBR28 was found to have a higher specific binding than [11C]PK11195 and it has been used to show microglia activation in animal models [8,9] and in clinical studies [10,11]. Several other radioligands have been developed [1], of which [11C]PBR28 is a radioligand with high affinity for the TSPO and showing a good ratio between specific and non-specific binding [8]. [11C]PBR28 was found to have a higher specific binding than [11C]PK11195 and it has been used to show microglia activation in animal models [8,9] and in clinical studies [10,11]. [11C]PBR28 is a promising radioligand for imaging neuroinflammation in animal models of human neurological diseases using small animal PET
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