In vivo preclinical PET/CT imaging of carbon-11-labeled aminoglycerol probe for the diagnosis of liver fibrosis.

Abstract

As an important membrane protein, aquaglyceroporin involves liver glycerol metabolism, which can be used to stage liver fibrosis. In this study, we synthesized a novel molecular probe carbon-11-labeled AR ([11C]AR) with aminoglycerol (AR), and evaluated its preclinical performance for liver fibrosis diagnosis by positron emission tomography/computed tomography (PET/CT) imaging in vivo. We developed a fully automatic synthesis procedure for the preparation of [11C]AR by radiolabeling glycerol analogue precursor AR with carbon-11. The liver uptake kinetics of [11C]AR was investigated using a rat model by the PET/CT scanner. The dynamic PET/CT scans were performed between the control group (n = 5) and experimental group (n = 25), which was divided into three subgroups (S1, S2 + S3, S4) based on the stages of liver fibrosis. The regions of interest (ROIs) of 20 pixels were drawn in the liver area on the reconstructed images. One-way analysis of variance and independent sample t test were used to analyze the statistical difference of the maximum standardized uptake value (SUVmax) among the groups at series of scanning time points (20s, 60s, 90s, 150s, 5min, 10min, 20min and 25min). The fully automatic synthesis of [11C]AR was successfully achieved with high synthesis efficiency (above 50%). The uptake of [11C]AR in progressive liver fibrosis tissues was significantly lower than that in healthy livers at all the imaging time points (P < 0.05), especially at early time points (before 10min p.i.). A cut-off SUVmax value (1.1) at 150s p.i. was set for discrimination progressive fibrosis from healthy liver. More experimental and healthy rats were tested with this new threshold to evaluate fibrosis situation. The sensitivity of detecting progressive fibrosis with [11C]AR was 100% in the second cohort. We demonstrated a new carbon-11-radiolabeled aminoglycerol PET/CT imaging probe [11C]AR for liver fibrosis diagnosis and staging, which may allow potential assessment of liver fibrosis stages in a rapid and noninvasive method.