Improved Derivation of Input Function in Dynamic Mouse [18F]FDG PET Using Bladder Radioactivity Kinetics

Abstract

Accurate determination of the plasma input function (IF) is essential for absolute quantification of physiological parameters in positron emission tomography (PET). However, it requires an invasive and tedious procedure of arterial blood sampling that is challenging in mice because of the limited blood volume. In this study, a hybrid modeling approach is proposed to estimate the plasma IF of 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) in mice using accumulated radioactivity in urinary bladder together with a single late-time blood sample measurement. Dynamic PET scans were performed on nine isoflurane-anesthetized male C57BL/6 mice after a bolus injection of [18F]FDG at the lateral caudal vein. During a 60- or 90-min scan, serial blood samples were taken from the femoral artery. Image data were reconstructed using filtered backprojection with computed tomography-based attenuation correction. Total accumulated radioactivity in the urinary bladder at late times was fitted to a renal compartmental model with the last blood sample and a one-exponential function that described the [18F]FDG clearance in blood. Multiple late-time blood sample estimates were calculated by the blood [18F]FDG clearance equation. A sum of four-exponentials was assumed for the plasma IF that served as a forcing function to all tissues. The estimated plasma IF was obtained by simultaneously fitting the [18F]FDG model to the time-activity curves (TACs) of liver and muscle and the forcing function to early (0-1 min) left-ventricle data (corrected for delay, dispersion, partial-volume effects, and erythrocyte uptake) and the late-time blood estimates. Using only the blood sample collected at the end of the study to estimate the IF and the use of liver TAC as an alternative IF were also investigated. The area under the plasma IFs calculated for all studies using the hybrid approach was not significantly different from that using all blood samples. [18F]FDG uptake constants in brain, myocardium, skeletal muscle, and liver computed by the Patlak analysis using estimated and measured plasma IFs were in excellent agreement (slope∼1; R2>0.983). The IF estimated using only the last blood sample drawn at the end of the study and the use of liver TAC as the plasma IF provided less reliable results. The estimated plasma IFs obtained with the hybrid method agreed well with those derived from arterial blood sampling. Importantly, the proposed method obviates the need of arterial catheterization, making it possible to perform repeated dynamic [18F]FDG PET studies on the same animal. Liver TAC is unsuitable as an input function for absolute quantification of [18F]FDG PET data.