Abstract

PurposeAn important issue in rodent imaging is the question whether a mixed population of male and female animals can be used rather than animals of a single sex. For this reason, the present study examined the test-retest stability of positron emission tomography (PET) with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) in male rats and female rats at different phases of the estrous cycle.ProceduresLong–Evans rats (age 1 year) were divided into three groups: (1) males (n = 6), (2) females in metestrous (low estrogen levels, n = 9), and (3) females in proestrous (high estrogen levels, n = 7). Two standard [18F]FDG scans with rapid arterial blood sampling were made at an interval of 10 days in subjects anesthetized with isoflurane and oxygen. Body temperature, heart rate, and blood oxygenation were continuously monitored. Regional cerebral metabolic rates of glucose were calculated using a Patlak plot with plasma radioactivity as input function.ResultsRegional metabolic rate of glucose (rCMRglucose) in male and female rats, or [18F]FDG uptake in females at proestrous and metestrous, was not significantly different, but females showed significantly higher standardized uptake values (SUVs) and Patlak flux than males, particularly in the initial scan. The relative difference between the scans and the test-retest variability (TRV) were greater in females than in males. Intra-class correlation coefficients (ICCs) of rCMRglucose, SUV, normalized SUV, and glucose flux were good to excellent in males but poor to moderate in females.ConclusionsBased on these data for [18F]FDG, the mixing of sexes in imaging studies of the rodent brain will result in an impaired test-retest stability of PET data and a need for larger group sizes to maintain statistical power in group comparisons. The observed differences between males and females do not indicate any specific gender difference in cerebral metabolism but are related to different levels of non-radioactive glucose in blood plasma during isoflurane anesthesia.

Highlights

  • IntroductionSijbesma J.W.A. et al.: Gender differences in FDG-positron emission tomography (PET) of the brain can be used, rather than animals from a single sex

  • An important issue in rodent imaging is the question whether a mixed population of female and male animalsSijbesma J.W.A. et al.: Gender differences in FDG-positron emission tomography (PET) of the brain can be used, rather than animals from a single sex

  • In order to assess the impact of gender mixing on the variability of preclinical positron emission tomography (PET) data, we here report the results of repeated, quantitative 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) scans of the brain of adult rats

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Summary

Introduction

Sijbesma J.W.A. et al.: Gender differences in FDG-PET of the brain can be used, rather than animals from a single sex. The inclusion of both sexes in study protocols might lead to a reduction of the number of surplus animals since experimental animals of the currently undesired sex would no longer need to be excluded. In order to assess the impact of gender mixing on the variability of preclinical positron emission tomography (PET) data, we here report the results of repeated, quantitative 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) scans of the brain of adult rats. Many reports on gender differences of glucose metabolism in the human brain have been published in the past decades, but the results have been conflicting. Other studies noted the mentioned difference in patients during motor activity but not in healthy subjects [4], or observed no differences between the sexes [5,6,7,8]

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