Abstract
Extracellular matrix (ECM) accumulation in liver fibrosis is caused by the activation of hepatic stellate cells (HSCs). The goal of this study was to develop a (99m)Tc-labeled N-acetylglucosamine (GlcNAc) that specifically interacts with desmin and vimentin expressed on activated HSCs to monitor the progression and prognosis of liver fibrosis using single-photon emission computed tomography (SPECT) imaging. Methods: GlcNAc-conjugated polyethylenimine (PEI) was first prepared and radiolabeled with (99m)Tc. Noninvasive SPECT imaging with (99m)Tc-GlcNAc-PEI was used to assess liver fibrosis in a carbon tetrachloride (CCl(4)) mouse model. The liver uptake value (LUV) of (99m)Tc-GlcNAc-PEI was measured by drawing the region of interest (ROI) of the whole liver as previously suggested. The LUV of the CCl(4) groups was compared with that of the olive oil group. Next, we estimated the correlation between the results of SPECT imaging and physiological indexes. After treatment with clodronate liposome, the LUV of (99m)Tc-GlcNAc-PEI in fibrotic mice was compared with that in control mice. Results:(99m)Tc-GlcNAc-PEI is a hydrophilic compound with high radiochemical purity (>98%) and good stability. It could specifically target desmin and vimentin on the surface of activated HSCs with high affinity (the K(d) values were 53.75 ± 9.50 nM and 20.98 ± 3.56 nM, respectively). The LUV of (99m)Tc-GlcNAc-PEI was significantly different between the CCl(4) and control groups as early as 4 weeks of CCl(4) administration (3.30 ± 0.160 vs 2.34 ± 0.114%/cc; P ˂ 0.05). There was a strong correlation between the LUV and Sirius Red quantification (R = 0.92, P ˂ 0.001). Compared with control, clodronate liposome treatment reduced the LUV of (99m)Tc-GlcNAc-PEI (4.62 ± 0.352 vs 2.133 ± 0.414%/cc; P ˂ 0.05). Conclusion:(99m)Tc-GlcNAc-PEI SPECT/CT was useful in assessing liver fibrosis and monitoring the treatment response.