Repeatable noninvasive measurement of mouse myocardial glucose uptake with 18F-FDG: evaluation of tracer kinetics in a type 1 diabetes model.
A noninvasive and repeatable method for assessing mouse myocardial glucose uptake with (18)F-FDG PET and Patlak kinetic analysis was systematically assessed using the vena cava image-derived blood input function (IDIF).


METHODS
Contrast CT and computer modeling was used to determine the vena cava recovery coefficient. Vena cava IDIF (n = 7) was compared with the left ventricular cavity IDIF, with blood and liver activity measured ex vivo at 60 min. The test-retest repeatability (n = 9) of Patlak influx constant K(i) at 10-40 min was assessed quantitatively using Bland-Altman analysis. Myocardial glucose uptake rates (rMGU) using the vena cava IDIF were calculated at baseline (n = 8), after induction of type 1 diabetes (streptozotocin [50 mg/kg] intraperitoneally, 5 d), and after acute insulin stimulation (0.08 mU/kg of body weight intraperitoneally). These changes were analyzed with a standardized uptake value calculation at 20 and 40 min after injection to correlate to the Patlak time interval.


RESULTS
The proximal mouse vena cava diameter was 2.54 ± 0.30 mm. The estimated recovery coefficient, calculated using nonlinear image reconstruction, decreased from 0.76 initially (time 0 to peak activity) to 0.61 for the duration of the scan. There was a 17% difference in the image-derived vena cava blood activity at 60 min, compared with the ex vivo blood activity measured in the γ-counter. The coefficient of variability for Patlak K(i) values between mice was found to be 23% with the proposed method, compared with 51% when using the left ventricular cavity IDIF (P < 0.05). No significant bias in K(i) was found between repeated scans with a coefficient of repeatability of 0.16 mL/min/g. Calculated rMGU values were reduced by 60% in type 1 diabetic mice from baseline scans (P < 0.03, ANOVA), with a subsequent increase of 40% to a level not significantly different from baseline after acute insulin treatment. These results were confirmed with a standardized uptake value measured at 20 and 40 min.


CONCLUSIONS
The mouse vena cava IDIF provides repeatable assessment of the blood time-activity curve for Patlak kinetic modeling of rMGU. An expected significant reduction in myocardial glucose uptake was demonstrated in a type 1 diabetic mouse model, with significant recovery after acute insulin treatment, using a mouse vena cava IDIF approach.
Division of Cardiology, National Cardiac PET Centre, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
Stephanie L
SL
Thorn
Robert A
RA
deKemp
Tyler
T
Dumouchel
Ran
R
Klein
Jennifer M
JM
Renaud
R Glenn
RG
Wells
Michael H
MH
Gollob
Rob S
RS
Beanlands
Jean N
JN
DaSilva
D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000000981:diagnostic imaging* / Q000378:metabolism*; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D006321:Heart / Q000000981:diagnostic imaging*; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D009206:Myocardium / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18
Patlak; myocardial glucose uptake; positron emission tomography; streptozotocin; test–retest repeatability