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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 (&gt;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.

Desmin- and vimentin-mediated hepatic stellate cell-targeting radiotracer 99mTc-GlcNAc-PEI for liver fibrosis imaging with SPECT

Desmin- and vimentin-mediated hepatic stellate cell-targeting radiotracer ^99mTc-GlcNAc-PEI for liver fibrosis imaging with SPECT