Limits...
Positron Emission Tomography studies with [11C]PBR28 in the Healthy Rodent Brain: Validating SUV as an Outcome Measure of Neuroinflammation.

Tóth M, Doorduin J, Häggkvist J, Varrone A, Amini N, Halldin C, Gulyás B - PLoS ONE (2015)

Bottom Line: A statistically significant correlation (r2 = 0.96; p < 0.01) was found between the VT and the SUV.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Centrum for Psychiatry Research, Stockholm, Sweden.

ABSTRACT

Unlabelled: 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.

No MeSH data available.


Related in: MedlinePlus

Correlation between VT and SUV of [11C]PBR28 in rats.Correlation between VT of [11C]PBR28 as calculated using two-tissue compartment modeling (2-TCM) (A+B) and Logan graphical analysis (C+D) [16], and the SUV of [11C]PBR28, for the averages of eight brain regions (A+C) and for the individual values for each rats for the eight brain regions (B+D).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4440816&req=5

pone.0125917.g006: Correlation between VT and SUV of [11C]PBR28 in rats.Correlation between VT of [11C]PBR28 as calculated using two-tissue compartment modeling (2-TCM) (A+B) and Logan graphical analysis (C+D) [16], and the SUV of [11C]PBR28, for the averages of eight brain regions (A+C) and for the individual values for each rats for the eight brain regions (B+D).

Mentions: The SUV of the time-frame of 57–63 minutes was calculated for the sampled rats and it was correlated to the VT (Fig 6). A high correlation between the average VT for eight different brain regions and the average SUV was found; r2 = 0.92 for 2-TCM (p<0.001) and r2 = 0.94 for Logan analysis (p<0.001). The individual correlations for each rat ranged from 0.87–0.95 (slope of 0.0099 to 0.0160) for 2-TCM and from 0.91 to 0.98 for Logan analysis (slope of 0.0148 to 0.1540). Additionally, a high correlation between the VT and the SUV was found when all the values of the individual rats were taken for the eight brain regions, instead of the average; r2 = 0.92 for 2-TCM (p<0.001) and r2 = 0.95 for Logan analysis (p<0.001).


Positron Emission Tomography studies with [11C]PBR28 in the Healthy Rodent Brain: Validating SUV as an Outcome Measure of Neuroinflammation.

Tóth M, Doorduin J, Häggkvist J, Varrone A, Amini N, Halldin C, Gulyás B - PLoS ONE (2015)

Correlation between VT and SUV of [11C]PBR28 in rats.Correlation between VT of [11C]PBR28 as calculated using two-tissue compartment modeling (2-TCM) (A+B) and Logan graphical analysis (C+D) [16], and the SUV of [11C]PBR28, for the averages of eight brain regions (A+C) and for the individual values for each rats for the eight brain regions (B+D).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4440816&req=5

pone.0125917.g006: Correlation between VT and SUV of [11C]PBR28 in rats.Correlation between VT of [11C]PBR28 as calculated using two-tissue compartment modeling (2-TCM) (A+B) and Logan graphical analysis (C+D) [16], and the SUV of [11C]PBR28, for the averages of eight brain regions (A+C) and for the individual values for each rats for the eight brain regions (B+D).
Mentions: The SUV of the time-frame of 57–63 minutes was calculated for the sampled rats and it was correlated to the VT (Fig 6). A high correlation between the average VT for eight different brain regions and the average SUV was found; r2 = 0.92 for 2-TCM (p<0.001) and r2 = 0.94 for Logan analysis (p<0.001). The individual correlations for each rat ranged from 0.87–0.95 (slope of 0.0099 to 0.0160) for 2-TCM and from 0.91 to 0.98 for Logan analysis (slope of 0.0148 to 0.1540). Additionally, a high correlation between the VT and the SUV was found when all the values of the individual rats were taken for the eight brain regions, instead of the average; r2 = 0.92 for 2-TCM (p<0.001) and r2 = 0.95 for Logan analysis (p<0.001).

Bottom Line: A statistically significant correlation (r2 = 0.96; p < 0.01) was found between the VT and the SUV.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Centrum for Psychiatry Research, Stockholm, Sweden.

ABSTRACT

Unlabelled: 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.

No MeSH data available.


Related in: MedlinePlus