Test-Retest Stability of Cerebral 2-Deoxy-2-[18F]Fluoro-D-Glucose ([18F]FDG) Positron Emission Tomography (PET) in Male and Female Rats

Jürgen W.A. Sijbesma, Aren van Waarde, David Vállez García, Hendrikus H. Boersma, Riemer H.J.A. Slart, Rudi A.J.O. Dierckx, Janine Doorduin

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Purpose: An 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. Procedures: Long–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. Results: Regional 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. Conclusions: Based 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.

Original languageEnglish
Pages (from-to)240-248
Number of pages9
JournalMolecular Imaging and Biology
Issue number2
Publication statusPublished - 15 Apr 2019


  • Estrogens
  • Gender differences
  • Regional cerebral metabolic rate of glucose
  • Small animal imaging
  • Test-retest stability

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