Modeling approach to estimate [18F]FDG blood sample measurements in mice by use of urinary bladder time-activity data

Accurate determination of the input function is essential for absolute quantification of physiological parameters in PET. However, it requires an invasive and tedious procedure of arterial blood sampling that is challenging in mice because of the limited blood volume and the small size of the blood vessels. Blood loss and surgical trauma may limit the same mouse to be studied longitudinally. In this paper, we proposed a modeling approach to estimate whole-blood sample measurements for 2-[¹⁸F]fluoro-2-deoxy-D-glucose ([¹⁸F]FDG) PET studies in mice by use of urinary bladder time-activity data and one blood sample taken at the end of the experiment. Six CL57BL/6 mice were injected with [¹⁸F]FDG, and serial blood samples were taken from the femoral artery via a surgically implanted catheter during small-animal PET scans. Image data were reconstructed by use of filtered backprojection with CT-based attenuation correction. The boundary of the urinary bladder was determined with the fused PET-CT image by adjusting the scaling of the PET image such that the bladder volume shown on the PET and CT images matched. The bladder time-activity data were then constructed frame-by-frame and fitted to a compartmental model in conjunction with a blood sample acquired near the end of the experiment and an one-exponential function that described the clearance of [¹⁸F]FDG in blood. Our results demonstrated that it is feasible to estimate [¹⁸F]FDG blood samples by use of urinary bladder time-activity data. The estimated samples obtained with the proposed method agreed well with those derived from the gold standard method of arterial blood sampling. More importantly, the proposed method obviates the need of arterial catheterization, making it possible to perform repeated studies on the same mouse.