Magnetic Resonance Gd-RGD Imaging Study of Hepatocellular Carcinoma with High and Low Metastatic Potential before and after Human Bone Marrow-derived Mesenchymal Stem Cell Intervention

Abstract

Background:Biotherapy based on human bone marrow-derived mesenchymal stem cells (BMSCs) is currently the focus of research, especially in the field of autologous stem cell transplantation. A novel type of metastasis-associated magnetic resonance (MR) molecular imaging probe was constructed, and the changes in metastasis and proliferation of hepatocellular carcinoma (HCC) before and after BMSC intervention were observed through MR imaging (MRI).Methods:Metastasis-associated MR molecular imaging probe, integrin αvβ3 ligand cRGD-PEG-DGL-DTPA-Gd (Gd-RGD), were constructed. After human BMSC intervention was performed for 6 weeks, tumor weight inhibition rates were calculated, and the RGD molecular probe was imaged through MRI with molecular imaging agent Gd-DTPA as control. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) in the MRI experiment were used as semi-quantitative indicators. Polymerase chain reaction method was performed to detect proliferation- and metastasis-associated indicators, transforming growth factor β-1 (TGFβ1), osteopontin (OPN), and integrin subunit αv and β3.Results:The highest tumor weight inhibition rates were observed 3 weeks after the BMSC transplantation. The MR Gd-RGD in the HCC tissues after the BMSC intervention showed less enhancement than Gd-DTPA. The Gd-DTPA MRI of control group had higher SNR and CNR than Gd-RGD MRI in the experimental groups (P < 0.05). For high metastatic potential hepatocellular carcinoma (MHCC97-H), significant differences were observed in the SNRs and CNRs of Gd-RGD MRI before and after the BMSC intervention (P < 0.05). For low metastatic potential hepatocellular carcinoma (MHCC97-L), the CNRs of Gd-RGD MRI were statistically different before and after BMSC intervention (P < 0.05). With regard to MHCC97-H, OPN, β3, and TGFβ1 expression significantly decreased after BMSC intervention (P < 0.05). In MHCC97-L and OPN, β3, TGFβ1, and αv expression after BMSC intervention decreased, and the difference was statistically significant (P < 0.05).Conclusions:The CNR index of MRI is a good indicator for distinguishing high- and low-metastatic potential HCC tissues. After BMSC transplantation of MRI through the two kinds of tracer, the SNR and CNR indexes can distinguish two kinds of high and low metastatic potential HCC tissues, and Gd-RGD imaging is more suitable in distinguishing the metastatic potential changes through BMSC intervention.

Micro-PET imaging of angiogenesis based on 18F-RGD for assessment liver metastasis in colorectal cancer

“…A SUVmean ratio of ≥ 1.551, a SUVmax ratio of ≥ 1.629 and a SUVmean ratio combined with SUVmax ratio of ≥ 0.759 identi ed as the best cut-off value to determine LoVo tumor from LS174T tumor. Our results were in line with the available published reference, as recently research showed that the contrast-to-noise (CNR) indexes of the Gd-RGD tracers in MRI was suitable for differentiating hepatocellular carcinoma (HCC) tissues with high metastatic potential from those with low metastatic potential [28]. However, the present study also had its limitation due to only two kinds of CRC cell lines with different metastatic potentials included in the comparative study.…”

The effect of bone marrow mesenchymal stem cells on highly metastatic MHCC97‑H hepatocellular carcinoma cells following OPN and TGFβ1 gene silencing

“…Thus, the decrease in metastatic potential following gene silencing in MHCC97-H was not associated with integrin α v β 3 expression, but was related to the decrease in OPN and TGFβ 1 expression. At lower levels, OPN and TGFβ 1 do not bind to integrin α v β 3 (39). Therefore, it is possible that low OPN and TGFβ 1 expression in MHCC97-H may reduce metastasis by other mechanisms.…”