A Novel Coacervate Embolic Agent for Tumor Chemoembolization.

Transcatheter arterial chemoembolization (TACE) has proven effective in blocking tumor-supplied arteries and delivering localized chemotherapeutic treatment to combat tumors. However, traditional embolic TACE agents exhibit certain limitations, including insufficient chemotherapeutic drug-loading and sustained-release capabilities, non-biodegradability, susceptibility to aggregation, and unstable mechanical properties. This study introduces a novel approach to address these shortcomings by utilizing a complex coacervate as a liquid embolic agent for tumor chemoembolization. By mixing oppositely charged quaternized chitosan (QCS) and gum arabic (GA), a QCS/GA polymer complex coacervate with shear-thinning property is obtained. Furthermore, the incorporation of the contrast agent Iohexol (I) and the chemotherapeutic doxorubicin (DOX) into the coacervate leads to the development of an X-ray-opaque QCS/GA/I/DOX coacervate embolic agent capable of carrying drugs. This innovative formulation effectively embolizes the renal arteries without recanalization. More importantly, the QCS/GA/I/DOX coacervate can successfully embolize the supplying arteries of the VX2 tumors in rabbit ear and liver. Coacervates can locally release DOX to enhance its therapeutic effects, resulting in excellent antitumor efficacy. This coacervate embolic agent exhibits substantial potential for tumor chemoembolization due to its shear-thinning performance, excellent drug-loading and sustained-release capabilities, good biocompatibility, thrombogenicity, biodegradability, safe and effective embolic performance, and user-friendly application.

The application of low temperature-storing tumor lumps in vitro in establishing VX2 liver cancer models:study of its modeling effect / 介入放射学杂志

Objective To compare the effect of using the fresh tumor lump and the recovered low temperature-storing VX2 tumor lump that have been frozen for different time to construct the rabbit HCC model.Methods Fish-like fresh VX2 tumor lumps were selected.After the peripheral necrotic tissue and muscle were removed,the tumor lumps were frozen at-80℃ for 3,5 and 7 months.Twenty New Zealand white rabbits were randomly divided into 4 groups.The rabbits in group A(control group)received fresh liver tumor lump implantation to construct in-situ VX2 rabbit HCC models.The rabbits in groups B,C and D(experimental groups)received implantation of the recovered low temperature-storing VX2 tumor lump which had been frozen at-80℃ for 3,5 and 7 months,respectively,to construct in-situ VX2 rabbit HCC models.Fourteen days after implantation,the modeling effect of tumor formation in each group was assessed.The proliferation,apoptosis of tumor cells and the angiogenesis were evaluated by immunofluorescence assay.Results The tumor formation rate of all group A,B,C and D was 100％.However,with the extension of cryopreservation time,the difference in tumor mass activity became larger after 5 months,and the necrotic area of liver tumor center became enlarged.Histological examination showed that there were no significant differences in the expressions of TUNEL,Ki67,HIF-α,VEGF and CD31 between group A and group B,while there were significant differences in the expressions of TUNEL,Ki67,HIF1-α,VEGF and CD31 between group A,B and group C,D.Conclusion The rabbit VX2 HCC model,which is constructed by implantation of recovered low temperature-storing VX2 tumor lump being frozen at-80℃ in vitro for a certain time,can be successfully established within 7 months.The difference in tumor mass activity between tumor lumps became larger after 5 months.But on the whole,the constructed rabbit VX2 HCC model can better preserve the tumor strain activity.This modeling technique can save manpower and material resources.(J Intervent Radiol,2024,33:269-274)

Comparative study of CT and MR guided microwave ablation in the treatment of para-vascular VX2 liver tumor model in rabbits.

Objective： To analyze the efficacy of microwave ablation (MWA) guided by computed tomography (CT) and 1.5T magnetic resonance (MR) in the treatment of VX2 para-vascular liver tumor model in rabbits. Materials and Methods Sixty para-vascular VX2 liver tumor models in rabbits were randomly divided into CT-guided microwave ablation group (CT group, n=35) and MR-guided microwave ablation group (MR group, n=35). The complete ablation rate, mean operation time, postoperative complication rate and mean survival time were compared between the two groups. Results In the CT group, the rate of complete ablation was 68.6% (24/35), and the mean operation time was 42.1 ± 9.7 minutes. Three cases had ascites and one case had abdominal wall injury. In the MR group, the rate of complete ablation was 94.2% (33/35), and the mean operation time was 53.4 ± 10.9 minutes. One case was complicated with ascites. No serious complications such as pneumothorax, liver abscess, pleural effusion and diaphragm perforation were found in both groups. Between the two groups, the difference in complete ablation rate was statistically significant (P=0.006 ＜ 0.05). A statistically significant difference can also be found in mean operation time (P ＜ 0.01). The follow-up time was 21 days after the operation. As for the postoperative complication rate (11.4% in the CT group and 2.9% in the MR group, P=0.353) and mean survival time (16.9 ± 1.8 days in CT group, 18.3 ± 2.3 days in the MR group, P=0.925), the differences were not statistically significant. Conclusion Compared with CT guidance, although the microwave ablation time under MR guidance was longer, the complete ablation rate under MR guidance was high, which proved that MR guidance was a more effective way of microwave ablation guidance and was worth promoting in the clinic. In this experiment, the postoperative complication rate was lower in the MR group, although the difference was not statistically significant, which may be related to the small sample size, and the subsequent study on the postoperative complication rate can increase the sample content.

Bevacizumab-loaded CalliSpheres beads: in vitro loading, release profiles and application in rabbit liver VX2 tumor model.

Background: Bevacizumab loaded drug-eluting beads have the potential to reduce TACE related VEGF expression. The purpose of this study was to investigate the in vitro loading, and release profiles of bevacizumab (BEV) loaded on Callispheres beads (CB) and its application in rabbit liver VX2 tumor model. Methods: CB with sizes of 100-300 um and 300-500 um were divided into 5 groups, respectively. BEV with different content was prepared for CB loading, releasing and detected in the solution at different time points. The diameters of CB in each group were measured under a light microscope to calculate the shrinkage rate. The rabbit with VX2 liver model were divided into control group, CB-TACE group, CB-TACE+BEV group, and BEV group. The data of blood test, CT image, HE and IHC staining were compared and analyzed. Results: The shrinkage rate of the 100-300 um CB was 2.6-7.2%, while the 300-500 um CB was 0.2-7.1%. The BEV-loaded CB (BEV-CB) has a burst release during the first hour and following gradually released with time. The release profiles of 100-300 um CB reach 34% in 24 hours, while the 300-500 um CB to 25.8%. BEV-CB with sizes of 100-300 um was chosen to perform transcatheter arterial chemoembolization (TACE). The results showed that BEV-CB-TACE not only gradually increased the content of BEV in serum and organ tissue but also reduced the level of VEGF in serum. Pathological results suggested that the expression of HIF-1 was elevated while VEGF and MVD decreased when compared to the other groups. Conclusion: In conclusion, this study confirms that Callispheres beads could efficiency loaded BEV. BEV-CB-TACE has a good safety and effectiveness, and its application could reduce the level of VEGF-A in serum in the treatment of VX2 tumors.

Precision of quantitative parameters of 18F-FDG PET/CT in a rabbit VX2 tumor model.

Background: The precision reflecting repeated measurement error of quantitative parameters of flourine-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) for evaluating the therapeutic effect of solid tumor can help observe whether a real biologic change in glucose metabolism occurred, or if the change was caused by errors before and after the treatment. Methods: A total of 18 VX2 tumor-bearing male New Zealand rabbits confirmed by pathology were used, three of which were used for determining the best scanning time point after injection and 15 for a precision experiment by repeating PET/CT scans for three consecutive days. The PET volume computer-assisted reading (PET VCAR) software (GE Healthcare) was used to analyze the standardized uptake value (SUV) and total lesion glycolysis (TLG) parameters. The lean body mass (LBM) to calculate the SUV corrected for lean body mass (SUL) parameters was measured using dual energy X-ray absorptiometry (DXA). The precision was represented as the coefficient of variation of root mean square (RMS-CV) and standard deviation of root mean square (RMS-SD). The least significant change (LSC) was also calculated when considering precision. Results: The precision of SUV parameters, including SUVmax, SUVmean and SUVpeak ranged from 18.3% to 18.8%, which was similar to that of the SUL parameters (18.0-18.4%). Using 80% confidence interval (CI), the LSC of SUVmax and SULpeak were 33.1% and 33.3%, respectively; using 95% CI, the LSC of SUVmax and SULpeak were 50.1% and 51.0%, respectively. Conclusions: This research established the method of precision in a rabbit VX2 tumor model, which can be used for monitoring changes to assess the effects of drug treatment on solid tumors in experimental studies with 18F-FDG PET/CT imaging.

intravoxel incoherent motion diffusion-weighted MRI assessing the effect of the vascular disrupting agent CA4P on VX2 liver tumors in rabbits.

OBJECTIVE: This study aimed to assess the response of combretastatin-A4-phosphate (CA4P) in rabbit VX2 liver tumors using intravoxel incoherent motion diffusion-weighted MRI (IVIM DW-MRI). METHODS: Forty rabbits with implanted VX2 liver tumors underwent baseline MRI and were then given 10 mg/kg CA4P (n=20) or saline (n=20). After 4 h, 10 rabbits from each group underwent an MRI examination and were then sacrificed. The remaining rabbits underwent MRI after 1, 3, and 7 days and were then sacrificed. Liver samples were processed for H&E and immunohistochemical staining. IVIM parameters (D, f, D*) were compared in the treatment and control groups, and the correlations of IVIM parameters with microvascular density (MVD) were determined. RESULTS: At 4 h, the two treatment groups had significantly different f and D* values (p<0.001), and these values were at their minimum in the treatment group. The treatment group had moderate correlations between MVD and f at 4 h (r=0.676, p=0.032) and 7 days (r=0.656, p=0.039) and with D* at 4 h (r=0.732, p=0.016) and 7 days (r=0.748, p=0.013), but no correlation was reported between MVD and f or D* in the control group (all P>0.05). CONCLUSION: IVIM DW-MRI is a sensitive imaging technique. It successfully evaluated the effect of CA4P on VX2 liver tumors in rabbits. The f and D* values correlated with MVD at 4 h and 7 days after using CA4P, indicating that these parameters have the potential to be used as indicators of tumor angiogenesis after treatment.

Renal and hepatic artery embolization with Pickering gel emulsion of lipiodol in rabbit.

OBJECTIVE: This research aimed to evaluate the feasibility of a novel liquid embolic agent Pickering gel emulsion of lipiodol (PGEL) for renal and hepatic artery embolization in the rabbit experimental model. METHODS: Embolization was performed in the right renal artery of 24 adult New Zealand White rabbits and 24 VX2 tumors in the left liver lobe. The rabbits were randomly allocated to four treatment groups (n = 6 per group): (A) normal saline (NS), (B) lipiodol, (C) 180-300 µm polyvinyl alcohol (PVA), and (D) PGEL. RESULTS: Renal artery embolization in normal rabbits and transarterial embolization (TAE) in VX2 tumor-bearing rabbits indicated that PGEL achieved a better embolization effect for a longer time than lipiodol and PVA. The tumor growth ratio of the PGEL group was significantly lower than that of the NS, lipiodol, and PVA groups at 3 (P < 0.001) and 7 (P < 0.001) days after embolization. In addition, hematoxylin and eosin and immunohistochemical staining revealed that the tumor necrosis ratio was higher in the PGEL group than in the NS, lipiodol, and PVA groups (P < 0.01), and the expression levels of HIF-1α, VEGF, and CD31 decreased after PGEL embolization compared with the lipiodol and PVA treatments. CONCLUSION: PGEL is an effective embolic material that provides immediate and total occlusion of the renal artery and may be a potential therapeutic embolic agent for TAE of HCC.

Nanoscale CaO2 materials for synergistic transarterial chemoembolization in a VX2 orthotopic rabbit liver cancer model.

Transcatheter arterial chemoembolization (TACE) is extensively used in the treatment of hepatocellular carcinoma (HCC), but its efficacy is usually limited to secondary tumor hypoxia and other progressive exacerbation of the abnormal tumor microenvironment (TME). Herein, we synthesized polyvinyl pyrrolidone (PVP)-coated CaO2 nanoparticles (CaO2 NPs) and applied them as a synergistic agent to improve the antitumor efficacy of TACE. After injection into the tumor, CaO2 NPs reacted with water to generate abundant oxygen, hydroxyl ions (OH-), and calcium ions (Ca2+), thereby relieving tumor hypoxia, neutralizing acid, and overloading Ca2+ to mediate antitumor effects. Moreover, the effect of chemotherapeutic drugs within the TACE was improved due to the modulated TME. CaO2 NPs efficiently regulated the TME and improved the antitumor effect of doxorubicin under hypoxia conditions in vitro. Compared to other groups, the TACE+CaO2 NPs group achieved the lowest tumor growth rate, highest tumor necrosis rate, lowest expression of histological markers associated with hypoxia and angiogenesis (HIF-α, VEGF, and CD31), and highest CD8+ T cell recruitment in vivo. Thus, these findings demonstrated that CaO2 NPs provide synergy for TACE therapy in the VX2 orthotopic rabbit liver cancer model, suggesting that they have a potential broad clinical application. STATEMENT OF SIGNIFICANCE: The efficacy of transcatheter arterial chemoembolization (TACE) for treatment of hepatocellular carcinoma is usually limited to secondary tumor hypoxia and other progressive exacerbation of the abnormal tumor microenvironment (TME). To address this issue, we synthesized CaO2 nanoparticles (CaO2 NPS) which would react with water to generate abundant oxygen, hydroxyl ions (OH-), and calcium ions (Ca2+), thereby relieving tumor hypoxia, neutralizing the acidic TME, and inducing Ca2+ overloading. The efficacy of CaO2 NPs in combination with TACE was investigated in an orthotopic rabbit liver cancer model, and the results showed the great synergetic antitumor effect of TACE and CaO2 NPs.

The correlation between multimodal radiomics and pathology about thermal ablation lesion of rabbit lung VX2 tumor.

Objective: To explore the correlation of CT-MRI pathology with lung tumor ablation lesions by comparing CT, MRI, and pathological performance of rabbit lung VX2 tumor after thermal ablation. Methods: Thermal ablation including microwave ablation (MWA) and radiofrequency ablation (RFA) was carried out in 12 experimental rabbits with lung VX2 tumors under CT guidance. CT and MRI performance was observed immediately after ablation, and then the rabbits were killed and pathologically examined. The maximum diameter of tumors on CT before ablation, the central hypointense area on T2-weighted image (T2WI) after ablation, and the central hyperintense area on T1-weighted image (T1WI) after ablation and pathological necrosis were measured. Simultaneously, the maximum diameter of ground-glass opacity (GGO) around the lesion on CT after ablation, the surrounding hyperintense area on T2WI after ablation, the surrounding isointense area on T1WI after ablation, and the pathological ablation area were measured, and then the results were compared and analyzed. Results: Ablation zones showed GGO surrounding the original lesion on CT, with a central hypointense and peripheral hyperintense zone on T2WI as well as a central hyperintense and peripheral isointense zone on T1WI. There was statistical significance in the comparison of the maximum diameter of the tumor before ablation with a central hyperintense zone on T1WI after ablation and pathological necrosis. There was also statistical significance in the comparison of the maximum diameter of GGO around the lesion on CT with the surrounding hyperintense zone on T2WI and isointense on T1WI after ablation and pathological ablation zone. There was only one residual tumor abutting the vessel in the RFA group. Conclusions: MRI manifestations of thermal ablation of VX2 tumors in rabbit lungs have certain characteristics with a strong pathological association. CT combined with MRI multimodal radiomics is expected to provide an effective new method for clinical evaluation of the immediate efficacy of thermal ablation of lung tumors.

Pi-inducedin-situaggregation of sevelamer nanoparticles for vascular embolization.

Decades have witnessed rapid progress of polymeric materials for vascular embolic or chemoembolic applications. Commercially available polymeric embolics range from gelatin foam to synthetic polymers such as poly(vinyl alcohol). Current systems under investigation include tunable, bioresorbable microspheres composed of chitosan or poly(ethylene glycol) derivatives,in situgelling liquid embolics with improved safety profiles, and radiopaque embolics that are trackablein vivo. In this paper, we proposed a concept of 'responsive embolization'. Sevelamer, clinically proved as an inorganic phosphate binder, was ground into nanoparticles. Sevelamer nanoparticle is highly mobile and capable of swelling and aggregating in the presence of endogenous inorganic phosphate, thereby effectively occluding blood flow in the vessel as it was administered as an embolic agent for interventional therapy. Moreover, citrated sevelamer nanoparticles delayed the aggregation, preferable to penetrate deeply into the capillary system. On the rabbit VX2 liver cancer model, both sevelamer particles aggregates occlude the tumor feeding artery, but backflow was found for the pristine one, thereby citrate passivation of sevelamer nanoparticles endows it have potential from 'bench to bedside' as a new type of vascular embolic.

CT perfusion imaging can detect residual lung tumor early after radiofrequency ablation: a preliminary animal study on both tumoral and peri-tumoral region assessment.

BACKGROUND: Radiofrequency ablation (RFA) is a minimally invasive procedure to treat lung cancer. Timely evaluation on residual lung tumor after RFA is crucial to the prognosis, hence, our objective is to assess CT perfusion (CTP) on detection of residual lung tumor early after RFA. METHODS: CTP imaging was performed in 24 lung VX2 tumor models 1 day before and within 1 hour after RFA. CTP maps with dual-input (n=24) and single-input [n=13, with predominant ground glass opacity (GGO) after RFA] models were generated using the maximal slope method. Regions of interest were independently placed on the maximal cross-sectional tumor before and after RFA and on GGO after RFA by two thoracic radiologists. The bronchial flow (BF), pulmonary flow (PF) and perfusion index (PI) were compared between pre-RFA and post-RFA images. The parameters (BF, PF and PI of tumor; PF of GGO) of the complete and incomplete RFA groups were compared based on nicotinamide adenine dinucleotide hydrogen (NADH) and TdT-mediated dUTP nick-end labeling (TUNEL) staining and were correlated with the microvascular density (MVD). RESULTS: The BF and PF decreased after RFA (all P values <0.03). The decrease in BF and PF (ΔBF and ΔPF) in the complete RFA group was higher (P=0.01; 0.02). The areas under the curve (AUC) of ΔBF and ΔPF at 14.85 and 17.25 mL/min/100 mL in determination of tumor with complete ablation were 0.80 and 0.78, respectively. ΔBF was positively correlated with MVD (P=0.046, r=0.468). PF of GGO with incomplete RFA was higher (P=0.001). The AUC of PF ≤29.4 mL/min/100 mL in determination of tumor with complete ablation was 0.99. CONCLUSIONS: CTP could detect residual lung tumor early after RFA in a rabbit model, which might provide a clinical solution to early treatment assessment after RFA.

Development of a Hepatic VX2 carcinoma model in rabbits using an improved minimally invasive method and evaluation with imaging examinations.

Context: The hepatic VX2 carcinoma model in rabbits has been widely used in interventional diagnosis and treatment research for hepatocellular carcinoma (HCC). However, traditional methods for developing this model all have their shortcomings. Aims: To develop an improved method to construct an animal model of hepatic VX2 carcinoma. Settings and Design: The puncture technique was used to obtain the VX2 tumor tissue. A tumor puncture-inoculation kit was designed and modified to implant the tumor tissue into the recipient rabbit's liver. Methods and Material: 18 New Zealand white rabbits were implanted with VX2 tumor tissue using the improved tumor puncture-inoculation kit under ultrasound guidance. Ultrasonography, contrast-enhanced computerized tomography, magnetic resonance imaging, and digital subtraction angiography were performed to evaluate tumor formation and imaging characteristics. Statistical Analysis: Statistical analysis was performed using SPSS software. Two groups were compared using Student's t-test analysis. Results: All rabbits tolerated VX2 tumor tissue implantation successfully. 17 out of the 18 experimental rabbits developed liver tumors, and one rabbit had abdominal tumor metastasis. The average volume of tumors was 39.47 mm3 and 460.1 mm3 (P < 0.001) on the 7th and 14th days after modeling, respectively. Imageological diagnosis showed that all tumors had abundant blood supply and typical imaging characteristics. Conclusions: This improved modeling method is easy to operate and less traumatic, with a high tumor formation rate, low metastasis rate, prominent tumor imaging characteristics, and high detection rate, which is expected to become a promising method for constructing rabbit liver tumor model.

Early Assessment of Response to Radiofrequency Ablation With CT Perfusion Imaging in Rabbit VX2 Liver Tumor Model.

OBJECTIVES: To discriminate viable tumors from benign periablational enhancement (BPE) in early stage after radiofrequency ablation (RFA) is a major confounding problem. The goal of this study is to evaluate quantitative assessment and diagnostic value of CT perfusion between viable tumors and BPE after RFA in the rabbit liver VX2 tumor model, with pathological results as the standard. METHODS: Twenty-eight VX2 liver tumors were treated with RFA, on days 1, 3, 7, and 14, seven rabbits were randomly chosen for CT perfusion and performed pathology examinations immediately. The perfusion parameters along with the profile of time-density curves (TDCs) and pseudo-color images of the parameters were observed in both BPE and viable tumors, then compared with the pathology results. The perfusion parameters included blood flow (BF), blood volume (BV), time to peak (TTP), permeability (P), arterial liver perfusion (ALP), portal venous perfusion (PVP) and hepatic perfusion index (HPI). RESULTS: A total of 26/28 rabbits successfully underwent CT perfusion, while 6/26 lesions were confirmed to be viable tumors. The TDCs of BPE were mainly speed-up platform curves (15/26), while the viable tumors showed mainly speed-up speed-down (3/6) and speed-up platform (2/6) curves. The PVP values were significantly higher, and the HPI values were significantly lower for BPE at all time points than viable tumors (P < 0.05). Both of PVP value and HPI value have high efficiency for the differential diagnosis of the viable tumors and BPE at each time point. These characteristics of CT perfusion parameters were consistent with pathological changes. CONCLUSIONS: The TDCs, PVP and HPI have the potential to indicate BPE and viable tumors effectively early after RFA treatment, the results were highly consistent with pathology. CT perfusion has advantages with great efficacy in monitoring the therapeutic effect early after RFA treatment.

Interventional real-time optical imaging guidance for complete tumor ablation.

The aim of this study was to develop an interventional optical imaging (OI) technique for intraprocedural guidance of complete tumor ablation. Our study employed four strategies: 1) optimizing experimental protocol of various indocyanine green (ICG) concentrations/detection time windows for ICG-based OI of tumor cells (ICG cells); 2) using the optimized OI to evaluate ablation-heat effect on ICG cells; 3) building the interventional OI system and investigating its sensitivity for differentiating residual viable tumors from nonviable tumors; and 4) preclinically validating its technical feasibility for intraprocedural monitoring of radiofrequency ablations (RFAs) using animal models with orthotopic hepatic tumors. OI signal-to-background ratios (SBRs) among preablation tumors, residual, and ablated tumors were statistically compared and confirmed by subsequent pathology. The optimal dose and detection time window for ICG-based OI were 100 µg/mL at 24 h. Interventional OI displayed significantly higher fluorescence signals of viable ICG cells compared with nonviable ICG cells (189.3 ± 7.6 versus 63.7 ± 5.7 au, P < 0.001). The interventional OI could differentiate three definitive zones of tumor, tumor margin, and normal surrounding liver, demonstrating significantly higher average SBR of residual viable tumors compared to ablated nonviable tumors (2.54 ± 0.31 versus 0.57 ± 0.05, P < 0.001). The innovative interventional OI technique permitted operators to instantly detect residual tumors and thereby guide repeated RFAs, ensuring complete tumor eradication, which was confirmed by ex vivo OI and pathology. In conclusion, we present an interventional oncologic technique, which should revolutionize the current ablation technology, leading to a significant advancement in complete treatment of larger or irregular malignancies.

Development of a 3D-Printed Navigational Template for Establishing Rabbit VX2 Lung Cancer Model.

BACKGROUND: The CT-guided percutaneous puncture-inoculation for establishing the rabbit VX2 lung cancer model (LCM) is time-consuming, requires repeated CT scans, and has a high complication rate. Therefore, this study aimed to develop a navigational template using 3D technology to provide an alternative method for establishing the model with improved success and complication rates. MATERIALS AND METHODS: Ideal pressure was determined using chest CT data from 15 anesthetized rabbits fitted with sphygmomanometer cuff around their chests. Subsequently, a preliminary 3D template with a square window and cross-sign to facilitate precise installation was designed. Using another 20 rabbits fixed with the preliminary template, an ideal common puncture point and parameter were determined, a navigational tunnel was set up on the template surface, and the final puncture navigational template was printed out. Eight-four rabbits (42/group) were assigned to the experimental (template-guided puncture) and control (traditional puncutre) groups and underwent VX2 tumor-fragment inoculation to validate the template. Differences in various parameters between two groups were analyzed. RESULTS: The ideal pressure was 30 mmHg. All rabbits were inoculated successfully and the template adequately fit the rabbit chest. The experimental group displayed significantly better operation time (198.93±36.64 vs 735.14±91.19 seconds); number of CT scans (0 vs 7.19±1.64); pneumothorax (11.9% vs 35.7%), chest seeding (16.7% vs 35.7%), and mid-lung field tumor-bearing (88.1% vs 59.5%) rates than the control group (all, P <0.05). The groups did not differ in rib injury, tumor volume or survival time (all, P > 0.05). CONCLUSIONS: We successfully developed a puncture navigational template, providing an alternative method for establishing the rabbit VX2 LCM.

Imaging features of microwave-ablated lesions of the VX2 tumors in rabbit lungs on computed tomography and magnetic resonance images and their correlations with pathological examination.

PURPOSE: This study aimed to explore the accuracy of different imaging methods for lesion volume estimation pre- and post-microwave ablation (MWA) as compared with that of pathological examination. METHODS: We used the VX2 cell line to establish the VX2 lung tumor model in rabbits, followed by MWA of the tumor. The imaging features of the VX2 tumors were documented. The volume of the tumors and the ablated lesions were measured and compared across imaging methods, using the pathological examination as reference. RESULTS: Tumors were successfully developed in 11 rabbits (age, 13.91 ± 1.38 weeks; weight, 2.15 ± 0.56 kg). The mean volume of the tumors was 2.05 ± 1.88 cm3. CT showed the strongest correlation with the pathologic examination results (r = 0.998, p<.001). MWA created three-layered structures that were delineated on MRI. The mean volume of the post-ablation lesion was 10.39 ± 8.93 cm3, and the measurement of the post-ablation volume on 3D-VIBE-T1WI showed the strongest correlation with the pathologic examination results (r = 0.991, p<.001). CONCLUSION: Both CT and MRI are capable of depicting lung tumors. In terms of post-ablation evaluation, MR images could provide more versatile information. The 3D-VIBE-T1WI sequence provides more precise lesion volume evaluation after ablation compared with other methods.

Changes in and effects of Kupffer cells on residual tumor after cryoablation in rabbit hepatic VX2 tumor.

OBJECTIVE: Cryoablation can directly kill tumor cells through sudden changes in temperature. It can also enhance lymphocyte function and cause distant tumor regression far from the ablation treatment area. In order to further explore the changes of immune function after cryoablation, the changes of Kupffer cells (KCs), the main immune cells in the liver, and their effects on untreated tumors in vivo were studied. METHODS: Rabbit VX2 liver cancer models were constructed. The growth of liver tumors was confirmed by ultrasound after transplantation for 3 weeks. Fifteen Japanese white rabbits were divided into a tumor control group and cryoablation group. Cryoablation group was treated with cryoablation of a single or partial tumor. Histologic and immunohistochemical changes of the treatment area and untreated tumor area before and after cryoablation were observed, and the phagocytic function changes of KCs around the untreated area and treatment area were observed by electron microscopy. RESULTS: Cryoablation areas showed necrosis, infiltration of inflammatory cells (including KCs), and fibrosis of tissue. The number of inflammatory cells in the unfrozen tumor area was increased in the same treated rabbit. There was a significant difference in the maximum diameter of unfrozen tumors between the frozen group and control group at 15th days after cryoablation (P<0.05), while the difference was not obvious at the 3rd and 7th day (P>0.05). Electron microscopy showed that the number of debris fragments engulfed by KCs around the tumor after cryoablation was significantly higher than that of the control group. In the same rabbit, we compared the amount of debris between tissue surrounding the unfrozen area and around the cryoablation area. There was a significant difference on the 3rd day after cryoablation, P=0.043, while there was no significant difference on the 7th day, P=0.348. CONCLUSION: After cryoablation, inflammatory cells aggregated around the cryoablated area. The activity of KCs had been increased and the function of phagocytosis enhanced. KCs had a certain inhibitory effect on the untreated tumor in the same animal at the early stage (within 15 days), but it was not enough to restrain the growth of the untreated tumors.

Irreversible electroporation ablation against subcutaneously implanted VX2 tumors in rabbits: findings of shearwave ultrasound elastography.

PURPOSE: This study aimed to evaluate stiffness changes of rabbit subcutaneous VX2 tumors before and after irreversible electroporation (IRE) ablationby shearwave ultrasound elastography (SWE). METHODS: IRE was performed on 20 subcutaneously implanted VX2 tumors in rabbits (R-SIVX2). Tumor stiffness was measured by SWE at different time points (before IRE,120minutes after IRE,7 days after IRE and 14 days after IRE). RESULTS: Before IRE, the mean stiffness (Emean) of tumors was (10.45 ± 1.07) KPa. 120 minutes after I RE, the Emean of tumors obviously rose to (70.53 ± 9.87) KPa. 7 days after IRE, the Emean of tumors decreased to (40.22 ± 9.01) KPa. 14 days after IRE, the Emean of tumors was (15.17 ± 1.00) KPa. A clear boundary was observed between the ablation area and the normal tissues in the pathological results. CONCLUSIONS: The stiffness of the VX2 tumors experienced a first rise process and tend to be normal in the procedure of IRE. SWE could provide tissue stiffness information of different IRE ablation period as a non-invasive method.

Survival Benefit of Radiofrequency Ablation with Intratumoral Cisplatin Administration in a Rabbit VX2 Lung Tumor Model.

PURPOSE: This study evaluated the survival benefit of a combination therapy with radiofrequency ablation (RFA) and intratumoral cisplatin (ITC) administration for lung tumors by using a rabbit VX2 tumor model. MATERIALS AND METHODS: Experiments were approved by the institutional animal care committee. VX2 tumor suspension was injected into the lungs of Japanese white rabbits under CT guidance to create a lung tumor model. Thirty-two rabbits bearing a transplanted VX2 lung tumor were randomly assigned to four groups of eight: control (untreated); RFA alone; ITC alone; and RFA with ITC. All treatments were performed one week after tumor transplantation. Kaplan-Meier survival curves were compared by the log-rank test. RESULTS: The median survival time was 24.5 days (range 17-33 days) in the control group, 40 days (30-80 days) in the RFA alone group, 31.0 days (24-80 days) in the ITC alone group, and not reached (53-80 days) in the RFA with ITC group. The median survival was significantly longer with the RFA/ITC combination compared to the control group (P < 0.001), RFA alone (P = 0.034), and ITC alone (P = 0.004). The survival time after RFA alone was also significantly longer than that of the control group (P < 0.001). There was no significant difference in tumor size or the rate of pneumothorax between each group. CONCLUSION: RFA prolonged the survival of rabbits with lung VX2 tumors when combined with ITC.

Establishment of a vx2 bone tumor model in rabbit tibia / 中国组织工程研究

BACKGROUND: Many methods have been developed to establish a rabbit VX2 tumor model, but the reliability of each method has not been explored. In order to develop a reliable method, we made some improvements based on the existing methods. OBJECTIVE: To investigate the reliability of rabbit VX2 tumor tissue block implantation and cell suspension via modified and traditional implantation to make the rabbit tibia VX2 tumor model. METHODS: Forty healthy adult New Zealand white rabbits were randomly divided into two groups. Group A was treated with tissue block implantation for tibia VX2 tumor modeling, and group B was treated with cell suspension for tibia VX2 tumor modeling. Modified and traditional implantation was performed on the left and right tibia of the experimental animals, respectively. One hour after successful modeling, ultrasound examination of the puncture site was performed to determine whether there is hematoma. All experimental animals were sacrificed at 3 weeks. X-ray examination of the bilateral tibia was performed to confirm the tumor growth range. Tumor tissue and soft tissue around the puncture site were taken for general and pathological observation to compare the size of the tumor and identify whether there is tumor cell metastasis. RESULTS AND CONCLUSION: One rabbit died in the tissue block group, and all the experimental animals in the cell suspension group survived. X-ray examination indicated the tumors in the tissue block group invaded the cortex, but the tumors in the cell suspension group did not invade the cortex. Gross observation revealed that the tumor volume of the tissue block group was greater than that of the cell suspension group. In the tissue block group, there were one and seven cases of hematoma around the puncture site at 1 hour after modified and traditional implantation, respectively. In the cell suspension group, there were two and nine cases of hematoma around the puncture site at 1 hour after modified and traditional implantation, respectively. Pathological examination showed that local tumor invasion was found in 1 and 8 cases in the tissue block group as well as in 2 and 11 cases in the cell suspension group at 3 months after modified and traditional implantation, respectively. Our findings indicate that the tissue block implantation method is easier and more convenient than the cell suspension method for making rabbit VX2 bone tumors, and the tumor invasion rate of the tissue block implantation method is lower than that of the cell suspension method. Improved tissue block implantation can effectively reduce the tumor invasion rate during modeling.