TY - JOUR
T1 - Test-Retest Stability of Cerebral 2-Deoxy-2-[18F]Fluoro-D-Glucose ([18F]FDG) Positron Emission Tomography (PET) in Male and Female Rats
AU - Sijbesma, Jürgen W.A.
AU - van Waarde, Aren
AU - Vállez García, David
AU - Boersma, Hendrikus H.
AU - Slart, Riemer H.J.A.
AU - Dierckx, Rudi A.J.O.
AU - Doorduin, Janine
N1 - Funding Information:
During this research project, JWAS was appointed as a PhD student (and biotechnician) at the University of Groningen. The study expenses were covered by university funding. We thank the Central Committee on Animal Experiments of the Netherlands (CCD) which asked us to perform the experiments described in this paper, and Bettina Bernard (Munich, Germany) who provided assistance during the scans.
Publisher Copyright:
© 2018, The Author(s).
PY - 2019/4/15
Y1 - 2019/4/15
N2 - 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.
AB - 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.
KW - Estrogens
KW - Gender differences
KW - Regional cerebral metabolic rate of glucose
KW - Small animal imaging
KW - Test-retest stability
UR - http://www.scopus.com/inward/record.url?scp=85049639613&partnerID=8YFLogxK
U2 - 10.1007/s11307-018-1245-4
DO - 10.1007/s11307-018-1245-4
M3 - Article
C2 - 29987619
AN - SCOPUS:85049639613
SN - 1536-1632
VL - 21
SP - 240
EP - 248
JO - Molecular Imaging and Biology
JF - Molecular Imaging and Biology
IS - 2
ER -