Measurement of cerebral glucose metabolic rates in the anesthetized rat by dynamic scanning with 18F-FDG, the ATLAS small animal PET scanner, and arterial blood sampling.
Rodent models and genetically altered mice have recently become available to study many human diseases. A sensitive and accurate PET scanner for small animals would be useful to evaluate treatment of these diseases in rodent models. To examine the feasibility of performing quantitative PET studies, we performed dynamic scans with arterial blood sampling in anesthetized rats with the ATLAS (Advanced Technology Laboratory Animal Scanner) small animal PET scanner developed at the National Institutes of Health and (18)F-FDG and compared activities determined by PET scanning with those obtained by direct tissue sampling.


METHODS
Dynamic PET scans after a bolus of approximately 48 MBq (1.3 mCi) (18)F-FDG were performed in rats anesthetized with isoflurane. Arterial blood sampling was performed throughout the scanning period. At 60 min the rat was killed, and the brain was rapidly removed and dissected into 5 structures (thalamus [TH], cortex [CX], brain stem [BS], cerebellum [CB], and half brain). Activity in the tissue samples was compared with the mean activity of the last 5 min of calibrated PET data.


RESULTS
Plasma activity peaked at approximately 0.2 min and then cleared rapidly. Brain activity initially rose rapidly; the rate of increase then progressively slowed until activity was approximately constant between 30 and 60 min. Recovery coefficients (MBq/mL in PET images)/(MBq/mL in tissue samples) were 0.99 +/- 0.04, 0.90 +/- 0.19, 1.01 +/- 0.24, 0.84 +/- 0.05, and 1.01 +/- 0.17, respectively, in TH, CX, BS, CB, and half brain (mean +/- SD, n = 6-9). Cerebral glucose utilization determined by Patlak analyses of PET data measured 30-60 min after injection of (18)F-FDG was 31.7 +/- 5.2, 23.9 +/- 4.8, 29.9 +/- 5.0, 39.3 +/- 7.3, and 28.1 +/- 4.6 micro mol/100 g/min (mean +/- SD, n = 9) in TH, CX, BS, CB, and whole brain, respectively. These results are consistent with a previous (14)C-deoxyglucose study of the isoflurane-anesthetized rat.


CONCLUSIONS
Expected values for glucose metabolic rates and recovery coefficients near unity suggest that quantitatively accurate dynamic (18)F-FDG brain imaging can be performed in the rat with arterial blood sampling and the ATLAS small animal PET scanner.
Shimoji
Kazuaki
K
Positron Emission Tomography Department, Clinical Center, National Institutes of Health, Bethesda, Maryland, USA.
Ravasi
Laura
L
Schmidt
Kathleen
K
Soto-Montenegro
Maria Luisa
ML
Esaki
Takanori
T
Seidel
Jurgen
J
Jagoda
Elaine
E
Sokoloff
Louis
L
Green
Michael V
MV
Eckelman
William C
WC
D000758:Anesthesia; D000818:Animals; D001786:Blood Glucose / Q000032:analysis*; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D001931:Brain Mapping / Q000379:methods*; D019544:Equipment Failure Analysis; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D005947:Glucose / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D011865:Radioisotope Dilution Technique; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed / Q000295:instrumentation* / Q000379:methods
D001786:Blood Glucose; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D005947:Glucose