Estimation of the 18F-FDG Input Function in Mice by Use of Dynamic Small-Animal PET and Minimal Blood Sample Data

摘要

Derivation of the plasma time–activity curve in murine small-animal PET studies is a challenging task when tracers that are sequestered by the myocardium are used, because plasma time–activity curve estimation usually involves drawing a region of interest within the area of the reconstructed image that corresponds to the left ventricle (LV) of the heart. The small size of the LV relative to the resolution of the small-animal PET system, coupled with spillover effects from adjacent myocardial pixels, makes this method reliable only for the earliest frames of the scan. We sought to develop a method for plasma time–activity curve estimation based on a model of tracer kinetics in blood, muscle, and liver.MethodsSixteen C57BL/6 mice were injected with ¹⁸F-FDG, and approximately 15 serial blood samples were taken from the femoral artery via a surgically inserted catheter during 60-min small-animal PET scans. Image data were reconstructed by use of filtered backprojection with CT-based attenuation correction. We constructed a 5-compartment model designed to predict the plasma time–activity curve of ¹⁸F-FDG by use of data from a minimum of 2 blood samples and the dynamic small-animal PET scan. The plasma time–activity curve (TACp) was assumed to have 4 exponential components (TACP = A1e^λ1t + A2e^λ2t + A3e^λ3t − (A1 + A2 + A3) e^λ4t) based on the serial blood samples. Using Bayesian constraints, we fitted 2-compartment submodels of muscle and liver to small-animal PET data for these organs and simultaneously fitted the input (forcing) function to early small-animal PET LV data and 2 blood samples (~10 min and ~1 h).