Preparation of a glypican-3-targeting hepatocellular carcinoma MR probe and its molecular imaging in HepG2 cells / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To prepare a glypican-3 (GPC3)-targeting hepatocellular carcinoma MR molecular probe and to evaluate its targeting specificity using HepG2 cells.</p><p><b>METHODS</b>Poly(lactic-co-glycolic acid) (PLGA) nanoparticles were prepared by a double emulsion solvent evaporation method, and the surfaces were connected with anti-GPC3 mono-antibody and paramagnetic substance Gd3+. The physical properties of the probes were investigated using fluorescence microscopy, electron microscopy, Malvern particle size analysis, inductively coupled plasma atomic emission spectroscopy (ICP-AES) and 1.5T MR imaging. The specificity of the probes to target cultured HepG2 cells was determined by laser confocal microscopy. The signal characteristics, including signal-to-noise ratio (SNR), after co-incubation with HepG2 cells were analyzed by 1.5T MR imaging. Significance of differences between multiple groups (target group, non-target group, and control group) was assessed by one-way analysis of variance, and between two groups was assessed by the LSD-t test. A difference was considered to be statistically significant at P less than 0.05.</p><p><b>RESULTS</b>The GPC3-targeting hepatocellular carcinoma MR molecular probes were successfully prepared. The nanoparticles had a spherical shape, size of 495 +/- 17.5 nm, uniform size distribution, good dispersibility, no obvious aggregation, and could significantly increase the T1 signal. Using the ICP-AES measurement, 1 mol PLGA carried about 12 mol Gd3+, and as the Gd3+ concentration increased, the T1 signal increased. The prepared MR molecular probes could specifically target HepG2 cells, and could increase the T1 signal. The SNR value of the target group was 3.45 +/- 0.21, of the non-target group was 1.43 +/- 0.07, and of the control group was 1.12 +/- 0.03. The SNR value of the target group was significantly higher than that of the non-target group and the control group (P less than 0.05); there was no significant difference between the non-target group and the control group (P more than 0.05).</p><p><b>CONCLUSION</b>PLGA nanoparticles, anti-GPC3 mono-antibody and paramagnetic Gd3+ can be used to successfully prepare GPC3-targeting hepatocellular carcinoma MR molecular probes which are capable of specifically targeting HepG2 cells in vitro and being detected by 1.5T MR imaging. These MR molecular probes may represent a useful noninvasive imaging method for detecting early hepatocellular carcinoma in vivo.</p>

Preparation and in vitro study of a high molecular weight contrast agent targeting hepatoma cells / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To prepare a specific high molecular weight polymer contrast agent capable of specifically targeting hepatocarcinoma cells (HCC) and to investigate its affinity in vitro using HepG2 cells.</p><p><b>METHODS</b>The high molecular weight polymer polylactic-co-glycolic acid (PLAG)-COOH was prepared by the double emulsion technique. PLAG-COOH microbubbles were combined with glypican-3 (GPC3) antibody to generate HCC targeting high molecular polymer ultrasound contrast agents by the carbodiimide method. The affinity for HCC cells was confirmed by measuring attachment to cultured HepG2 cells by flow cytometry and comparing the results with the properties observed for non-targeted high molecular weight polymer ultrasound contrast agents.</p><p><b>RESULTS</b>The average diameter of the targeted high molecular weight polymer ultrasound contrast agents was (800+/-10) nm. In vitro targeting of HepG2 cells showed that many of the targeted high molecular weight polymer ultrasound contrast agents attached tightly to the cell surface and that the GPC3-PLGA has a particularly strong targeting ability.</p><p><b>CONCLUSION</b>A HCC-specific high molecular contrast agent, GPC3-PLGA, was synthesized and evidenced a strong targeting ability towards HepG2 cells in vitro. This new agent may be exploited to improve diagnosis of liver cancer at the molecular level.</p>

1H magnetic resonance spectroscopy in the evaluation of high intensity focused ultrasound ablation for primary liver cancer / 中华肝脏病杂志

To investigate the clinical value of 1H magnetic resonance spectroscopy (1H MRS) in the evaluation of high intensity focused ultrasound (HIFU) ablation for primary liver cancer. Routine magnetic resonance sequences, contrast-enhanced magnetic resonance imaging and respiratory-triggered single voxel point resolved spectroscopy sequence (PRESS) were performed on 24 patients with primary liver cancer before and after HIFU ablation. A respiratory-triggered axial T2 weighted imaging (T2WI) was used as localizer for PRESS. Spectroscopy data was transmitted to a personal computer and was post-processed with a custom software (Saker, provided by Ning Jing, an engineer in GE Healthcare). It would be considered "technical success" if the baselines of spectra were stable and main metabolites were without overlapping and could be identified. Integral areas of choline (Cho) peak at 3.2 parts per million (ppm) and lipid (Lip) peak at 1.3 ppm were measured, and the choline to lipid (Cho/Lip) ratios were calculated. The differences of areas of Cho, Lip peak and Cho/Lip ratios before and after HIFU ablation were compared by using paired samples t test, and a P value of less than 0.05 was considered statistically significant. The technical success rate of 1H-MRS was 87.50% (42/48). Integral areas of Cho peak and Lip peak of 20 patients with satisfied spectra were measured, and the Cho/Lip ratios were calculated. The Integral area of Cho peak decreased from 34 597+/-6 802 before HIFU ablation to 6 372+/-2 466 after HIFU ablation (t = 18.02, P less than 0.01). The Integral area of Lip peak increased from 147 948+/-16 317 before HIFU ablation to 149 069+/-16 345 after HIFU ablation (t = -15.11, P less than 0.01). The Cho/Lip ratio decreased from 0.23+/-0.03 before HIFU ablation to 0.04+/-0.02 after HIFU ablation (t = 25.32, P less than 0.01). 1H-MRS could provide information of metabolites changes of primary liver cancer after HIFU ablation and could be used as a complementary sequence to other magnetic resonance sequences to evaluate all around primary liver cancer after HIFU ablation.

CT image of liver secondary lymphoma / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To analyze the CT image characteristics of liver secondary lymphoma.</p><p><b>METHODS</b>The medical records of 13 patients were reviewed. There were 12 non-Hodgkin lymphoma cases and 1 Hodgkin lymphoma case. Abdomen CT scan was performed in all cases, plain scan and enhanced CT scan were performed in 11 cases, plain CT scan was performed in 2 cases.</p><p><b>RESULTS</b>Of the 13 cases, 11 were nodular type, 1 was diffuse type, and 1 was mixed type. Plain CT scan showed low density, enhanced CT showed circular enhancement in 1 case, mild to midrange delayed enhancement in 1 case, midrange enhancement in 1 case, mild enhancement in 2 cases, blood vessel floating sign in 3 cases, no enhancement in 6 cases.</p><p><b>CONCLUSIONS</b>The characteristics of liver secondary lymphoma CT image of liver secondary lymphoma includes blood vessel floating sign and enhancement.</p>

The application of 3D liver acquisition volume acceleration integrated with array spatial sensitivity encoding technique in liver dynamic-enhancement scanning / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To evaluate the application of 3D liver acquisition volume acceleration (3D-LAVA) integrated with array spatial sensitivity encoding technique (ASSET) in liver dynamic-enhancement scanning.</p><p><b>METHODS</b>One hundred forty-seven patients underwent conventional plain and contrast enhancement liver MR imaging. 3D-LAVA and 2D fast spoiled gradient recalled echo were used for contrast enhancement liver MR scanning in 90 and 57 patients respectively. In the 3D-LAVA group, integrated ASSET was used in 72 out of the 90 patients. Of the 57 patients who underwent examinations using 2D fast spoiled gradient recalled echo, portal vein CE-MRA was performed on 20. The ability of 3D-LAVA to detect the lesions and the advantage to shorten the acquisition time after integrating with ASSET were analyzed. Original images of 60 patients in the 3D-LAVA group were processed using MIP to illustrate the anatomy of the portal vein. They were compared with those shown by CE-MRA to evaluate the illustration abilities of the two approaches.</p><p><b>RESULTS</b>3D-LAVA is more sensitive than 2D-FSPGR in detecting metastatic hepatic carcinomas. In the 3D-LAVA group integrated with ASSET, earlier and peak arterial phase images were acquired in 34 cases; and earlier, peak and late arterial phase images were acquired in 23 cases. The illustrations of the portal vein anatomy by 3D-LAVA were similar to those shown by portal vein CE-MRA.</p><p><b>CONCLUSION</b>3D-LAVA integrated with ASSET can obtain higher quality multi-phase dynamic enhancement images of the liver in a shorter time, and in the meantime also shows the vascular anatomy.</p>