Reproducibility of 5-HT_2A receptor measurements and sample size estimations with [¹⁸F]altanserin PET using a bolus/infusion approach

Abstract

Purpose

To determine the reproducibility of measurements of brain 5-HT_2A 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.

Methods

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.

Results

In cortical brain regions with a high density of 5-HT_2A 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.

Conclusion

This study demonstrates that [¹⁸F]altanserin PET with a bolus/infusion design has very low variability, particularly in larger brain regions with high 5-HT_2A receptor density. Moreover, partial volume correction considerably reduces the sample size required to detect regional changes between groups.