Implanted VX2 Tumor Research Articles

A preliminary study on the establishment of a cyst and cystic neoplasm tissue-mimicking model.

The present experimental models of cystic diseases are not adequate and require further investigation. In this study, a new way of producing a tissue-mimicking model of cysts and cystic neoplasms was evaluated. To simulate cysts and cystic neoplasms, ex vivo rabbit normal bladders and VX2-implanted tumor bladders were produced, fixed, and embedded in agarose gel. The samples were classified into four groups based on tumor features and the maximal transverse diameter of the rabbit bladder, which were assessed using computer tomography (CT) imaging and statistically analyzed. Statistical analysis was performed using Statistical Package for the Social Sciences (SPSS) software. The t-test was used for analyzing enumeration data. Twenty-one rabbit bladders (21/24) were successfully removed and prepped for this experiment, comprising eleven normal bladders (11/24) and ten implanted with VX2 tumors (10/24). The gelling ingredient used to form the visualization and fixation matrix was agarose at a concentration of 4 g/200 mL. The temperature of the agarose solution was kept constant at 40-45°C, which is the optimal temperature range for ex vivo normal bladder and implanted VX2 tumor bladder insertion. The average time required to embed and fix the bladders in agarose gel was 45.0 ± 5.2 minutes per instance. The gel-fixing matrix's strength and light transmittance were enough for building the models. We created an experimental tissue-mimicking model of cysts and cystic neoplasms with stable physicochemical features, a safe manufacturing method, and high repeatability. These models may be used to assist with cystic lesion diagnosis and treatment techniques.

99mTc-radiolabeled composites enabling in vivo imaging of arterial dispersal and retention of microspheres in the vascular network of rabbit lungs, liver, and liver tumors.

PurposeSelective internal radiation therapy (SIRT) is an effective treatment option for liver tumors, using Y-90-loaded polymer microspheres that are delivered via catheterization of the hepatic artery. Since Y-90 is a beta emitter and not conveniently imaged by standard clinical instrumentation, dosimetry is currently evaluated in each patient using a surrogate particle, 99mTechnetium-labeled macroaggregated albumin (99mTc-MAA). We report a new composite consisting of 99mTc-labeled nanoparticles attached to the same polymer microspheres as used for SIRT, which can be imaged with standard SPECT.MethodsCarbon nanoparticles with an encapsulated core of 99mTc were coated with the polycation protamine sulfate to provide electrostatic attachment to anionic polystyrene sulfonate microspheres of different sizes (30, 12, and 8 µm). The in vivo stability of these composites was determined via intravenous injection and entrapment in the capillary network of normal rabbit lungs for up to 3 hours. Furthermore, we evaluated their biodistribution in normal rabbit livers, and livers implanted with VX2 tumors, following intrahepatic artery instillation.ResultsWe report distribution tests for three different sizes of radiolabeled microspheres and compare the results with those obtained using 99mTc-MAA. Lung retention of the radiolabeled microspheres ranged from 72.8% to 92.9%, with the smaller diameter microspheres showing the lowest retention. Liver retention of the microspheres was higher, with retention in normal livers ranging from 99.2% to 99.8%, and in livers with VX2 tumors from 98.2% to 99.2%. The radiolabeled microspheres clearly demonstrated preferential uptake at tumor sites due to the increased arterial perfusion produced by angiogenesis.ConclusionWe describe a novel use of radiolabeled carbon nanoparticles to generate an imageable microsphere that is stable in vivo under the shear stress conditions of arterial networks. Following intra-arterial instillation in the normal rabbit liver, they distribute in a distinct segmented pattern, with the smaller microspheres extending throughout the organ in finer detail, while still being well retained within the liver. Furthermore, in livers hosting an implanted VX2 tumor, they reveal the increased arterial perfusion of tumor tissue resulting from angiogenesis. These novel composites may have potential as a more representative mimic of the vascular distribution of therapeutic microspheres in patients undergoing SIRT.

Abstract B69: Antitumor effects of combining hemocoagulase with the blocking-microvascular action of microbubbles enhanced ultrasound cavitation on rabbit VX2 liver tumors

Abstract Substantial effort is being directed toward investigating the use of microbubble enhanced ultrasound cavitation (MEUC) to promote penetrate vascular wall and disrupting circulation in liver tumor. In this study we propose and investigate a new method for combining MEUC with hemocoagulase (HC) atrox, which is effectively a vascular targeting to induce embolism effects and combine these with an antiangiogenic treatment strategy. HC was administered was inserted precisely into the tumor under the guidance of real- time ultrasound with a 21-gauge needle. MEUC were conducted at1 MHz frequency probe (with a 400-cycle pulse length and a pulse repetition frequency of 9 Hz) at peak positive pressure of 1 MPa in combination with the commercial microbubble agent SonoVue. MEUC treatments were performed on 10 min on and off periods and HC was administered for 1KU. Rabbits were implanted VX2 tumor mass to establish a liver tumor model. 7 days after tumor implantation, rabbits presented with single liver tumor were randomly divided into 4 study groups: (1) control group were given injections of saline use micro- pump intravenously. (2) HC only injection. (3) MEUC treatment. (4) MEUC+HC treatment. The MEUC induced an acute reduction of blood flow as confirmed with contrast enhanced ultrasound (CEUS) imaging. QontraXt software quantitative analysis time intensity curve (TIC) of the tumor blood perfusion and microvascular changes. The MEUC+HC treatment group showed significant growth inhibition relative to the MEUC-only (p < 0.01) and HC-only treatment groups (p < 0.01). These results indicate the feasibility of a new approach to combining microbubble enhanced ultrasound cavitation with hemocoagulase. Citation Format: Qian Yang, Peng Tang, Liwen Liu, Shuping Ge, Xiaodong Zhou. Antitumor effects of combining hemocoagulase with the blocking-microvascular action of microbubbles enhanced ultrasound cavitation on rabbit VX2 liver tumors. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2016 Oct 20-23; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2017;5(3 Suppl):Abstract nr B69.

Preparation of thin-slice gross specimens in rabbit VX2 colorectal cancer model

Objective To invest the preparation of thin-slice gross specimens in rabbit VX2 colorectal cancer (CRC) model in order to provide the observation platform for experimental study in CRC. Methods Fifteen New Zealand white rabbits were implanted VX2 tumor piece into the colonic (13 rabbits) or rectal (2 rabbits) wall. Enhanced CT was performed weekly for 4-6 weeks after inoculation to determine the presence of CRC or metastases. Once CRC or metastases occurred or 6 weeks after implantation, the rabbits were sacrificed regardless of the presence or absence of a CRC or metastases on the CT images. The animals were then frozen in a freezer in the supine position as CT imaging. After 24 hours, the frozen rabbits were cut in the coronal plane into 2 mm- (2 rabbits), 3 mm- (10 rabbits), and 5 mm (3 rabbits)-thick slices using a motorized saw with 1.2 mm-thick saw blade. Each slice of the specimens was photographed by number at each interval (0-5 min, 10-15 min, and >20 min, respectively) and then placed in 10% phosphate-buffered formaldehyde for subsequent pathologic examination. Results Total of 182 slices (range: 15-20 slices, mean: 18.2 slices) of specimens were obtained using 3 mm-cut in 10 rabbits with 2 slices of damage resulted in an intact rate of 98.9% (180/182 slices), 40 slices (range: 11-14 slices, mean: 13.3 slices) for 5 mm- cut in 3 rabbits without slices of damage, and 45 slices (range: 21-24 slices, mean: 22.5 slices) for 2 mm-cut in 2 rabbits with 32 slices of damage resulted in an intact rate of 28.9% (13/45 slices). Comparison of intact rates both in 2 mm-versus (vs) 3 mm- and 5 mm-cut was all statistically significant (P=0.009, 0.002, respectively), but 3 mm-vs 5 mm-cut was statistically insignificant (P=0.964). Photography had a distinct gradation within 10-15 min, in which the anatomic structures between organs was immovable. However, the photographic gradation was not clear within 0-5 min because of a frozen layer on the surface of the specimen. Conversely, the anatomic structures occurred displacement over 20 min owing to the thaw of the specimen. The successful inoculation rate was 66.7% (10/15 rabbits). Specifically, 2 inoculated tumors were found in 3 rabbits for 5 mm-cut with 1 liver metastasis (6 mm) and 6 nodes (1 involved node), 7 inoculated tumors in 10 rabbits for 3 mm-cut with 2 lung metastases (range: 7-10 mm) and 29 nodes (7 involved nodes), respectively.3 mm-cut presented more nodes than that of 5 mm-cut (mean: 4.1 vs. 3.0 nodes) and complete metastasis. Conclusion Thin-slice gross specimens in rabbit VX2 CRC model could be obtained when 3 mm-cut was used in this study, which may provide an effectively experimental platform for tumor staging in animal model. Key words: Cancer, colorectal; Rabbit model; Gross specimen, thin-slice; Preparation

Antitumor Effects of Combining Hemocoagulase with the Blocking Microvascular Action of Microbubbles Enhanced Ultrasound Cavitation on Rabbit Vx2 Liver Tumor

Substantial effort is being directed toward investigating the use of microbubble enhanced ultrasound cavitation (MEUC) to promote penetrate vascular wall and disrupting circulation in liver tumor. In this study we propose and investigate a new method for combining MEUC with hemocoagulase (HC) atrox, which is effectively a vascular targeting to induce embolism effects and combine these with an antiangiogenic treatment strategy. Rabbits were implanted VX2 tumor mass to establish a liver tumor model. 7 days after tumor implantation, rabbits presented with single liver tumor were randomly divided into 4 study groups: (1) control group were given injections of saline use micro- pump intravenously. (2) HC only injection. (3) MEUC treatment. (4) MEUC+HC treatment. The MEUC induced an acute reduction of blood flow as confirmed with contrast enhanced ultrasound (CEUS) imaging. QontraXt software quantitative analysis time intensity curve (TIC) of the tumor blood perfusion and microvascular changes. HC was administered was inserted precisely into the tumor under the guidance of real- time ultrasound with a 21-gauge needle. MEUC were conducted at1 MHz frequency probe (with a 400-cycle pulse length and a pulse repetition frequency of 9 Hz) at peak positive pressure of 1 MPa in combination with the commercial microbubble agent SonoVue. MEUC treatments were performed on 10 min on and off periods and HC was administered for 1KU. Post MEUC+HC treatment at 1 h and 7-day, the parameters of TIC including peak value, RBV and AUC were measured using CEUS were significantly lower than that found in the other treatment groups. The MEUC+HC treatment group showed significant growth inhibition relative to the MEUC-only and HC-only treatment groups. The MEUC+HC treatment group showed significant growth inhibition relative to the MEUC-only (p < 0.01) and HC-only treatment groups (p < 0.01). No damage was observed in the surrounding normal tissues. These results indicate the feasibility of a new approach to combining microbubble enhanced ultrasound cavitation with hemocoagulase.

Echo Decorrelation Imaging of Rabbit Liver and VX2 Tumor during In Vivo Ultrasound Ablation

In open surgical procedures, image-ablate ultrasound arrays performed thermal ablation and imaging on rabbit liver lobes with implanted VX2 tumor. Treatments included unfocused (bulk ultrasound ablation, N = 10) and focused (high-intensity focused ultrasound ablation, N = 13) exposure conditions. Echo decorrelation and integrated backscatter images were formed from pulse-echo data recorded during rest periods after each therapy pulse. Echo decorrelation images were corrected for artifacts using decorrelation measured prior to ablation. Ablation prediction performance was assessed using receiver operating characteristic curves. Results revealed significantly increased echo decorrelation and integrated backscatter in both ablated liver and ablated tumor relative to unablated tissue, with larger differences observed in liver than in tumor. For receiver operating characteristic curves computed from all ablation exposures, both echo decorrelation and integrated backscatter predicted liver and tumor ablation with statistically significant success, and echo decorrelation was significantly better as a predictor of liver ablation. These results indicate echo decorrelation imaging is a successful predictor of local thermal ablation in both normal liver and tumor tissue, with potential for real-time therapy monitoring.

Early treatment response to sorafenib for rabbit VX2 orthotic liver tumors: evaluation by quantitative contrast-enhanced ultrasound.

The aim of our study was to investigate the application of contrast-enhanced ultrasound (CEUS) and its quantification analysis for the prediction of early treatment response of sorafenib on rabbit VX2 liver tumor model. Rabbits were implanted VX2 tumor mass to establish a liver tumor model. Fourteen days after tumor implantation, rabbits presented with single liver tumor were randomly divided into two groups. Rabbits in treatment group were given by gavage once a day for 14 days with sorafenib suspension at a dose of 30 mg/kg, whereas rabbits in control group were given saline by gavage of the same volume. CEUS was performed before treatment and 3, 7, 14 days after treatment for the analysis of tumor size, enhancement pattern, and necrosis range. The time intensity curve (TIC) was used to obtain quantitative parameters of enhancement patterns. Before sorafenib administration, tumor volumes ranged from 0.24 to 0.75 cm(3) (mean 0.49 ± 0.18 cm(3)) in treatment group and 0.24 to 0.44 cm(3) (mean 0.30 ± 0.12 cm(3)) in control group. The dynamic enhancement patterns of tumors were homogeneous hyper-enhancement (n = 8), heterogeneous hyper-enhancement (n = 4), and peripheral rim-like enhancement (n = 2). All tumors of the treatment group presented with peripheral rim-like enhancement with large necrotic area after sorafenib administration, whereas tumors of the control group showed heterogeneous hyper-enhancement (n = 5) and peripheral rim-like enhancement (n = 2). There was a significant difference in area under the curve (AUC) before and after sorafenib treatment (P = 0.045). CEUS may be of value in the evaluation of early therapeutic response after sorafenib administration.

The role of internal fixation for long bone metastasis prior to impending fracture: an experimental model

BackgroundPatients with long bone metastasis have many therapeutic options, including surgery. However, the appropriate time for surgical intervention and the use of internal fixation prior to impending fracture remains controversial. The purpose of this study was to establish a long bone metastatic model with internal fixation, and to determine whether prophylactic internal fixation for long bone metastasis prior to impending fracture would affect bone destruction, tumor progression, and mortality. Materials and methodsWe implanted VX2 tumor cells into the tibiae of 45 rabbits divided equally into three groups: internal fixation, control, and sham groups. Rabbits were monitored by X-ray and computed tomography, and blood serum levels were examined every 2weeks. ResultsComputed tomography data revealed significantly higher bone destruction in rabbit tibiae in the sham and control groups compared with those in the fixation group; there were volumetric bone losses of 0.2, 0.4, and 2.3% in the fixation, sham, and control groups, respectively, at 3weeks, which increased to 1.2, 2.5, and 6.1% at 5weeks. Rabbits in the fixation group showed significantly prolonged survival (64.5±13.5days) in comparison with rabbits in the sham group (50.3±11.6days) and control group (38.2±4.9days). ConclusionOur results suggest that prophylactic internal fixation may hinder bone destruction and tumor progression, thus extending the survival period for patients with long bone metastasis.

Histotripsy of Renal Implanted VX-2 Tumor in a Rabbit Model: Investigation of Metastases

To compare the number and density of lung metastases in histotripsy-treated and control subjects. Histotripsy is a noninvasive, nonthermal, pulsed ultrasound technology that produces targeted mechanical tissue fractionation. Histotripsy ablation of renal implanted VX-2 tumor has been previously demonstrated; however, concerns have been raised that mechanical forces associated with histotripsy might result in unwanted metastatic dissemination of tumor. VX-2 tumor was implanted into the left kidneys of New Zealand White rabbits. Twenty rabbits were treated with histotripsy on day 13; 8 were maintained as controls. All rabbits underwent left nephrectomy on day 14. Lungs were harvested and processed for histopathologic inspection on day 19. Whole-mount coronal lung sections were examined to determine the number of metastases and metastatic density. Tumors grew after implantation in all 28 cases and were localized with ultrasound in 19 of 20 subjects before treatment. Histology confirmed fractionation of tumor in all treatment rabbits. The number of lung metastases (88.7 vs 72.5; P = .29) and the metastatic density (8.9 vs 7.0 mets/cm(2); P = .22) were not statistically different between treatment and control rabbits. Histotripsy of renal implanted VX-2 tumor in an in-vivo rabbit model did not produce a statistically significant increase in number or density of lung metastasis. Data suggesting a trend toward increased metastases after histotripsy are overwhelmed by the high baseline rate of metastases in this aggressive tumor model. Further investigation using less aggressive tumor models is indicated to clarify this relationship.

Histotripsy of VX-2 Tumor Implanted in a Renal Rabbit Model

Histotripsy is an extracorporeal focused ultrasound (US) technology that uses controlled cavitation to induce nonthermal mechanical tissue fractionation. Feasibility of histotripsy ablation of normal renal tissue in an in vivo rabbit model has previously been demonstrated. Our specific objective in this study was to characterize the histologic effects of histotripsy on VX-2 tumor implanted in the kidneys of an in vivo rabbit model. VX-2 tumor was implanted below the renal capsule in 15 New Zealand white rabbits. Two weeks after implantation, tumors were localized with diagnostic US imaging. Targeted volumes within the observed tumor were treated with short (3 micros) pulses of 1 MHz acoustic energy at a repetition frequency of 300 Hz. Twenty tumors were treated with histotripsy and 7 served as tumor controls. Three normal kidneys were also treated with histotripsy. Kidneys and lungs were harvested, grossly inspected, and processed for histopathologic analysis. Real-time US imaging confirmed presence of cavitation during all histotripsy treatments. Examination of tumor and kidney specimens revealed 100% tumor growth with an average tumor diameter of 7 mm (range 2-12). In 16 of 20 tumors treated with histotripsy, acellular zones of debris and finely disrupted cellular architecture were present on histology. Kidneys harvested 24 hours after treatment revealed an extensive inflammatory reaction. Transcutaneous application of histotripsy to implanted VX-2 tumor in rabbit kidney produced fractionation of malignant tissue. These findings support the further study and development of histotripsy for potential oncologic application.

Functional Computed Tomographic Quantification of Angiogenesis in Rabbit VX2 Soft-Tissue Tumor Before and After Interventional Therapy

Our purpose was to investigate the applicative value of multislice spiral computed tomography (CT) perfusion imaging on quantitative assessment of tumor angiogenesis before and after transcatheter arterial embolization and monitoring the early interventional therapeutic effect in malignant solid tumors. Sixteen New Zealand white rabbits successfully implanted VX2 tumor in the unilateral proximal thigh were divided into 2 groups (8 per group) at random and performed conventional CT plain scan and perfusion scan 14 days after implantation and 3 days after interventional therapy, respectively. The values of blood flow (BF), blood volume (BV), mean transit time (MTT), and permeability surface area product (PS) in VX2 tumors and normal muscles were computed after intravenous bolus administration of iodinated contrast medium, and the differences among them were analyzed. Meanwhile, correlative analysis between perfusion parameters and microvessel density (MVD) counts and average optical density (AOD) of vascular endothelial growth factor (VEGF) was done. Before interventional therapy, the values of BF, BV, MTT, and PS of the VX2 tumors in interventional group were 303.28 +/- 69.91 mL 100 g min, 7.02 +/- 3.10 mL 100 g, 1.99 +/- 0.28 seconds, and 65.88 +/- 9.38 mL 100 g min, respectively. Compared with the parametric values of normal muscular tissues, there were significant differences among them (F values were 4285.82, 1867.46, 413.04, and 698.42, respectively; P < 0.01). There were no significant differences of the above parametric values between the interventional group and the control group. Three days after interventional therapy, the values of BF, BV, MTT, and PS of the VX2 tumors in the interventional group were 7.53 +/- 2.37 mL 100 g min, 1.20 +/- 0.23 mL 100 g, 3.29 +/- 0.57 seconds, 4.01 +/- 1.51 mL 100 g min, respectively. Compared with the parametric values of preinterventional therapy and the control group, there were significant differences among them (P < 0.01). In addition, there was a good positive correlation between BF, BV, PS, and MVD, and AOD of VEGF (r > 0.7, P < 0.05) in VX2 tumors; however, there was no significant correlation between MTT and MVD (P > 0.05), and there was significant negative correlation between MTT and AOD of VEGF (r = -0.78, P < 0.05). Multislice spiral CT perfusion imaging is a functional imaging technique that provides useful, quantitative assessment to tumor angiogenesis, blood perfusion, and vascular permeability, which can evaluate the early interventional therapeutic effect in malignant solid tumors invasively and accurately.

The feasibility of local harmonic motion imaging for the guidance and control of focused ultrasound surgery

A local harmonic motion (LHM) can be generated within the tissues by the periodic induction of radiation force using a focused ultrasound (FUS) transducer. Tissue motion can then be tracked by collecting RF signals during the excitation using a separate transducer. Finally, displacement estimates can be obtained by cross-correlating the collected RF signals. The characteristics of the induced LHM depend on the local elastic properties of the tissues making it an attractive tool for imaging and therapy control applications. LHM measurements have been obtained in vivo on rabbit muscle and it was observed that the amplitude of the motion was significantly reduced after coagulation. LHM was successfully used to spatially detect the presence of the coagulation lesions within the tissues as a drop in LHM amplitude. It was also possible to detect the location of an implanted VX2 tumor when a spatial scan was performed as the LHM amplitude was lower inside the tumor because of an increased stiffness. Measurements of LHM during tissue heating using FUS reflected the changes in stiffness and revealed the apparition of coagulation showing the potential of these measurements as an alternative control for the FUS exposure. [Work supported by NIH GrantR33 CA102884 and CRC.]

In vivo feasibility of local harmonic motion imaging and its use for thermal surgery control

A local harmonic motion can be generated within the tissues by the periodic induction of radiation force using a focused ultrasound (FUS) transducer. Tissue motion can then be tracked by collecting rf signals during the excitation using a separate transducer. Finally, displacement estimates can be obtained by cross‐correlating the collected rf signals. The characteristics of the induced LHM depend on the local elastic properties of the tissues making it an attractive tool for imaging and therapy control applications. LHM measurements have been obtained in vivo on rabbit muscle and it was observed that the amplitude of the motion was significantly reduced after coagulation. LHM was successfully used to spatially detect the presence of the coagulation lesions within the tissues as a drop in LHM amplitude. It was also possible to detect the location of an implanted VX2 tumor when a spatial scan was performed as the LHM amplitude was lower inside the tumor because of an increased stiffness. Measurements of LHM during tissue heating using FUS reflected the changes in stiffness and revealed the apparition of coagulation showing the potential of these measurements as an alternative control for the FUS exposure. [Work supported by NIH Grant R33 CA102884 and the Canadian Research Chair Program.]

Liver tumors: MR imaging of radioactive holmium microspheres--phantom and rabbit study.

To investigate the use of magnetic resonance (MR) imaging in the administration and biodistribution of holmium-loaded poly(L-lactic acid) microspheres (Ho-PLLA-MS) in liver tumors. MR imaging measurements were obtained in phantoms, three ex vivo rabbit livers, and four livers in living rabbits. When applicable, measurements were compared with those on scintigraphic images. The transverse relaxivity R2* of the Ho-PLLA-MS was determined in a phantom study. The in vivo animal experiments were performed by using rabbits with an implanted VX2 tumor. Detection of passing Ho-PLLA-MS to estimate lung shunting was performed in a scaled model of the vena cava. In the ex vivo liver experiments, the feasibility of real-time MR imaging during administration of microspheres was demonstrated. The in vivo rabbit experiments demonstrated that MR imaging can depict radioactive, nonradioactive, and decayed Ho-PLLA-MS after treatment for as long as they remain in the body. Furthermore, this study showed the ability of dynamic MR imaging to detect single doses of passing Ho-PLLA-MS. Ho-PLLA-MS used for internal radionuclide therapy can be imaged clearly in vivo with MR imaging.

Hypertonic saline-augmented radiofrequency ablation of the VX-2 tumor implanted in the rabbit kidney: a short-term survival pilot study

Objectives. The increased incidental detection of small (less than 4 cm) renal tumors has stimulated investigations of minimally invasive therapies. Radiofrequency energy is a relatively new and evolving technology that has been used for a variety of experimental and clinical applications. We evaluate the efficacy of hypertonic interstitial saline-augmented radiofrequency therapy to ablate a malignant VX-2 tumor implanted in a rabbit kidney, as measured by the completeness of tumor destruction and progression to metastasis. Methods. The VX-2 tumor was surgically implanted into the left lower pole parenchyma of 18 New Zealand white rabbit kidneys. Ten days after implantation, hypertonic interstitial saline-augmented radiofrequency ablation was performed (n = 12) using a radiofrequency therapy system (RFT, United States Surgical Corp.). A sham operation was performed on a control group (n = 6). Animals were humanely killed at 5, 10, and 15-day intervals, and the clinical response and effect of radiofrequency energy on the malignant renal tissue was assessed. Results. No postoperative complications were encountered. The mean size of the implanted VX-2 tumor was 1.87 cm 2. Kidneys in the treated group exhibited marked destruction of tumor tissue. Histologic analysis revealed coagulative necrosis of both malignant and normal renal tissue in the treated group. Three rabbits (1 control, 2 treated) died of metastatic disease. Conclusions. Coagulative necrosis of renal parenchyma and tumor tissue was clearly demonstrated after radiofrequency ablation using the RFT system. The aggressive growth pattern of the VX-2 tumor often resulted in progression to metastatic disease while precluding complete tumor ablation. Hypertonic saline-augmented radiofrequency ablation is a promising new technology for the management of small, locally confined, renal tumors and has the potential for use with a minimally invasive approach.

Assessment of liver and kidney enhancement with a perfluorocarbon vapor-stabilized US contrast agent

The authors evaluated the time-echogenicity response of liver, kidney, and implanted VX2 tumor after injection of a microbubble contrast medium and assessed use of an avascular lesion as an internal standard. Twenty-one New Zealand White rabbits were studied. To evaluate use of an internal standard and the dose-response relationship, nine rabbits with 7-day-old avascular liver lesions created by alcohol ablation received 0.1, 0.25, 0.5, and 1.0 mL of AF0145, a microbubble contrast agent. To evaluate tumor echogenicity, 12 rabbits implanted with VX2 tumor in the liver (six also underwent alcohol ablation) received 0.5 mL of AF0145. Videodensitometry was used to analyze echogenicity changes over 10 minutes. Echogenicity of the alcohol-ablated liver was not affected by contrast material administration. Liver and kidney echogenicity relative to ablation increased linearly with dose, peaking 1 minute after injection and decaying to baseline over 9 minutes. Contrast material administration defined the size and margins of VX2 lesions more clearly. In the arterial phase, the tumor rim was hyperechoic relative to surrounding liver, becoming isoechoic during the portal venous phase then hypoechoic during the late phase parenchymal phase. Lesions created by alcohol ablation can be used as an internal standard for quantitative analysis of adjacent tissues. AF0145 enhances perfused tissues, including vascular tumors, at gray-scale, real-time ultrasonography and enhances the liver.

Intra-arterial administration of heated albumin microspheres containing mitomycin C to rabbits with VX-2 tumor.

In an attempt to enhance antitumor effects, we prepared heated albumin microspheres containing mitomycin C (MMC). These MMC microspheres have an average diameter of 45 +/- 8 micrometers and contain about 5 per cent of MMC. The intra-arterial MMC microsphere treatment, for albino rabbits with implanted VX-2 tumor, increased remarkably the tissue MMC levels, compared to that with conventional MMC, and resulted in conspicuous antitumor efficacy. This approach to antitumor chemotherapy should be effective for selected patients with malignant tumor receiving a blood supply from an end-artery.