Reproducibility of 5-HT2A receptor measurements and sample size estimations with [18F]altanserin PET using a bolus/infusion approach
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To determine the reproducibility of measurements of brain 5-HT2A receptors with an [18F]altanserin PET bolus/infusion approach. Further, to estimate the sample size needed to detect regional differences between two groups and, finally, to evaluate how partial volume correction affects reproducibility and the required sample size.
For assessment of the variability, six subjects were investigated with [18F]altanserin PET twice, at an interval of less than 2 weeks. The sample size required to detect a 20% difference was estimated from [18F]altanserin PET studies in 84 healthy subjects. Regions of interest were automatically delineated on co-registered MR and PET images.
In cortical brain regions with a high density of 5-HT2A receptors, the outcome parameter (binding potential, BP1) showed high reproducibility, with a median difference between the two group measurements of 6% (range 5–12%), whereas in regions with a low receptor density, BP1 reproducibility was lower, with a median difference of 17% (range 11–39%). Partial volume correction reduced the variability in the sample considerably. The sample size required to detect a 20% difference in brain regions with high receptor density is approximately 27, whereas for low receptor binding regions the required sample size is substantially higher.
This study demonstrates that [18F]altanserin PET with a bolus/infusion design has very low variability, particularly in larger brain regions with high 5-HT2A receptor density. Moreover, partial volume correction considerably reduces the sample size required to detect regional changes between groups.
KeywordsAltanserin Reliability Sample size estimation Serotonin receptor Partial volume correction
We wish to thank Karin Stahr and the staff at the PET centre for their technical assistance, and The John and Birthe Meyer Foundation for the donation of the cyclotron and the PET scanner. This work was generously supported by the Danish Health Research Council, The Ludvig and Sara Elsass Foundation, The Hørslev Foundation, Director Jacob Madsen and Wife Olga Madsen’s Foundation, The Augustinus Foundation, The Beckett Foundation, The Foundation for Neurological Research, The A.P. Møller and Chastine McKinney Møller Foundation and The Lundbeck Foundation.
This investigation complies with the current laws in Denmark and was approved by the ethics committee in Copenhagen.
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