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PubMed2005

Acute and chronic swine rete arteriovenous malformation models: effect of ethiodol and glacial acetic acid on penetration, dispersion, and injection force of N-butyl 2-cyanoacrylate.

BACKGROUND AND PURPOSE: Liquid embolic agents are increasingly gaining importance in the embolization of cerebral arteriovenous malformations (AVMs). Currently, the most commonly used agent is N-butyl 2-cyanoacrylate (NBCA). Various NBCA mixtures, arterial hypotension, and Valsalva maneuver (increased positive end-expiratory pressure) during the injection of the acrylate have been used to address hemodynamic and architectural variations of an AVM; however, the precise in vivo polymerization, distribution, and kinetics of NBCA mixtures are unknown. We investigated the effect of different acrylate/Lipiodol mixtures and the addition of glacial acetic acid (GAA) on the penetration, dispersion, and injection force of NBCA. METHODS: A swine rete AVM model that has been described elsewhere was used for the embolization. In one subgroup of animals, embolization was performed immediately after construction of the AVM model. In a second subgroup, a chronic AVM model was used. GAA was added to the NBCA mixture to decrease the pH value of the solution and prolong the polymerization time. The addition of GAA allowed us to reduce the amount of Lipiodol, thereby reducing the viscosity of the mixture. A total of 30 swine were used for both the acute (n = 23) and chronic (n = 7) subgroups. The following mixtures of Lipiodol/NBCA and GAA (% vol/%vol + microL) were used for embolization: 80/20 + 0; 50/50 + 0; 50/50 + 5; 50/50 + 10; and 50/50 + 20. A total of six retia per mixture were used for the analysis. Glue injection pressure profiles were recorded in each experiment. High-resolution radiographic images obtained from the harvested retia were used to correlate the dispersion and depth of glue penetration with the AVM hemodynamics. The effect of different amounts of GAA on the glue dispersion and depth of penetration of the mixtures was also studied. RESULTS: Using the same pressure gradients, less viscous NBCA + GAA mixtures led to a deeper nidal penetration. The addition of 20 microL of GAA resulted in a three times higher penetration and dispersion of the NBCA mixture that was more homogenous. CONCLUSION: The viscosity of the liquid embolic agent used is an important limiting factor for an AVM embolization. Reducing the amount of Lipiodol improves nidus penetration. Quicker polymerization can be overcome by adding GAA, which reduces the pH of the mixture.

Acetic Acid↗
PubMed1999

Microcatheter adhesion of cyanoacrylates: comparison of normal butyl cyanoacrylate to 2-hexyl cyanoacrylate.

PURPOSE: To compare the catheter adhesion properties of 2-hexyl cyanoacrylate (Neuracryl M), a new agent, to those of normal butyl cyanoacrylate (Histoacryl), the most widely used liquid acrylic agent for microcatheter embolization. MATERIALS AND METHODS: 2-hexyl cyanoacrylate (Neuracryl M1) was tested in pure form and mixed with either a proprietary polymerization retardant/contrast agent (Neuracryl M2) or ethiodized oil (Ethiodol). Histoacryl was tested in pure form and mixed with Ethiodol. The cyanoacrylate mixtures were injected through microcatheters into wells partially filled with heparinized whole blood. The cyanoacrylates were allowed to polymerize around the microcatheter tips for 1-3 minutes. The microcatheters were then pulled at a constant rate until they were extracted from the polymerized cyanoacrylates. The peak forces required for extraction were recorded. RESULTS: The peak forces required to extract the microcatheters from either pure Histoacryl or Histoacryl mixed with 33% Ethiodol were significantly higher (P < .01; P < .05) than those for pure Neuracryl M1. When Neuracryl M1 and M2 were mixed together (as intended for clinical use), the force required for microcatheter extraction was significantly lower than that for either pure Histoacryl, Histoacryl mixed with 33% Ethiodol, or Neuracryl M1 alone (P < .01; P < .01; P < .01, respectively). The force required to extract microcatheters from the Neuracryl M1 and M2 mixture was not, however, significantly different from that of Histoacryl mixed with 50% Ethiodol. The force of extraction for the Neuracryl M1 and 50% Ethiodol mixture was below our ability to obtain precise measurements. CONCLUSION: When Neuracryl M1 was mixed with its proprietary polymerization retardant/contrast agent (Neuracryl M2), catheter adhesion was not significantly different from that of Histoacryl mixed with 50% Ethiodol, a mixture common in clinical use. When Neuracryl M1 was tested alone or mixed with Ethiodol (not intended by the manufacturer), catheter adhesion was significantly decreased relative to pure Histoacryl or equivalent mixtures of Histoacryl and Ethiodol.

Adhesiveness↗
PubMed1985

Liposomes as carriers of iodolipid radiocontrast agents for CT scanning of the liver.

We studied the potential of liposomes to deliver oil soluble radiocontrast agents to the liver and have developed a new preparation for CT liver scanning. The preparation consists of Ethiodol with a large amount of phospholipids. Nuclear magnetic resonance (NMR) spectroscopy was done for this lipid preparation, and the spectra show that the lipids are in the bilayer liposome configuration. Electron microscopy provides direct visualization of the liposomes. X-ray fluorescence measurements suggest that the Ethiodol is incorporated in the liposomes, and since no other particulate configurations are observed, we conclude that the Ethiodol is contained within the hydrophobic region of the liposomes. We used a GE CTT-8800 scanner and a rabbit model to study the liver uptake of the iodine from the Ethiodol. The iodine uptake in the liver was rapid and significant, and an increase in HU number of more than 40 was observed within 20 minutes after i.v. injection of 50 mg I/kg of body weight. Significant image enhancement was obtained. The iodine from the Ethiodol remained in the liver for several hours. Studies in rabbits with hepatic implants of the VX2-carcinoma show that while normal liver concentrates, areas of tumor do not concentrate the Ethiodol liposomes. Tumors not visible on ordinary scans become visible after administration of this combination. The advantages of this liposomal mode of radiocontrast agent administration are small particle size, rapid uptake in the liver, long retention times, a large increase in HU number and low iodine dose.

Animals↗
PubMed1985

Hepatocellular carcinoma detected by iodized oil. Use of anticancer agents.

Transcatheter arterial embolization (TAE) was performed in 97 patients with hepatocellular carcinoma. Ethiodol (iodized oil) containing an anticancer drug was infused via the hepatic artery followed by Gelfoam particles. The Ethiodol emulsion was selectively retained in the tumor vessels and also remained in the small daughter nodules that could not be detected by angiography or computed tomography (CT) prior to TAE. Ethiodol remained in the tumor for more than 1 year. Following TAE, main tumors and small daughter nodules appeared as areas of markedly high density on CT. In most patients there was a reduction in the tumor size following TAE, and serum alpha-fetoprotein levels were reduced in all patients whose initial levels had exceeded 400 ng/ml. This method is considered to be effective not only for treatment of hepatic tumor but also useful for evaluation of post-TAE changes in the tumor and diagnosis of small daughter nodules, due to the long-term accumulation of Ethiodol in tumor vessels.

Adult↗
PubMed1997

A comparison of locoregional depot and systemic preparations of 9-aminocamptothecin for treatment of liver metastases in a rat tumor model: superior antitumor activity of sustained-release preparation.

BACKGROUND: Locoregional therapy of hepatic-metastatic disease may overcome the limitations of systemic therapy by allowing tumor drug dose intensification without increasing systemic toxicity. This may result in improved efficacy. We have demonstrated that the novel topoisomerase I inhibitor 9-Aminocamptothecin (9-AC) when dissolved in Ethiodol acts as a sustained release preparation, with good antitumor activity. Its benefit as a depot hepatic intraarterial (i.a.) therapy for hepatic metastases was compared to systemic therapy with an aqueous colloidal dispersion (CD) preparation of 9-AC in a rat model, since a lack of demonstrable benefit of the locoregional therapy, would argue against further clinical evaluation. METHODS: Fisher rats underwent direct intraportal injection of 2 x 10(5) MADB106 adenocarcinoma cells and were treated 6 to 7 days later with: (a) bolus i.a. 9-AC (60 micrograms) in 60 microliters of Ethiodol; (b) bolus i.a. CD/9-AC (60 micrograms) in 200 microliters water; (c) bolus i.a. Ethiodol only (60 microliters), or (d) CD/9-AC (60 micrograms) in 200 microliters water, via a mini-osmotic pump pumping at 1 microliter/hr for 7 days intraperitoneally (i.p.). Livers were harvested 10 to 12 days later, and the number of metastases on the surface were counted blindly. RESULTS: Bolus hepatic i.a. 9-AC/Ethiodol was found to be significantly superior in reducing the number of hepatic metastases, when compared to the aqueous CD preparation administered in the same manner, or by continuous infusion via mini-osmotic pump i.p. (p < 0.01). Systemic therapy was also associated with substantial toxicity. CONCLUSIONS: These results suggest that locoregional therapy of hepatic neoplasms with 9-AC/Ethiodol would be associated with clinical efficacy far exceeding that associated with its systemic administration.

Animals↗
PubMed1983

Effect of arterial administration of high-molecular-weight anticancer agent SMANCS with lipid lymphographic agent on hepatoma: a preliminary report.

A clinical evaluation of arterial infusion of high-molecular-weight antitumor agent SMANCS dissolved in lipid lymphographic agent (thiodol) in 44 patients with mostly unresectable hepatoma is described. The treatment regimen demonstrated significant merits both therapeutically and diagnostically. Marked antitumor effects were shown in the decreased serum alpha-fetoprotein levels (86% of cases) and tumor size (95% of cases), and in survival period and histological findings. Furthermore, there was increased diagnostic sensitivity using CT scan, plain X-rays or ultrasound. The procedure of selective arterial administration of 3-4 mg of SMANCS in 3-4 ml of ethiodol per dose was simple to perform and was required only once every 3-4 weeks. Both ethiodol and the drug accumulated more selectively in tumor than in any other tissues and their activity remained for more than 3 weeks. Only minimal side-effects were associated with SMANCS and ethiodol during this study.

Adult↗
PubMed2005

Evaluation of targeted arterial delivery of the branched chain fatty acid 12-methyltetradecanoic acid as a novel therapy for solid tumors.

The purpose of this research was to evaluate the effects of targeted arterial delivery of the branched chain fatty acid 12-methyltetradecanoic acid (12-MTA) on the VX2 squamous cell carcinoma in rabbits. An intramuscular VX2 squamous cell carcinoma was induced at a single site in the right thigh of 39 New Zealand white rabbits. Approximately 10 days after inoculation, a 3-French catheter was introduced into the right common carotid artery and positioned using fluoroscopic guidance in the right deep femoral artery, which was the main, if not exclusive, artery supplying the tumor. Ethiodol alone (targeting agent), Ethiodol containing 12-MTA, or Ethiodol containing myristic acid was then injected through the catheter. Tumor growth and histopathology were evaluated 7-8 days after treatment. Caspase-3 activity was evaluated 2 days after therapy, and tumor tissues were assayed for eicosanoid metabolites 2 and 7 days after treatment to assess the effects of the branched chain fatty acid on the lipoxygenase (LOX) and cyclooxygenase-2 (COX-2) enzyme systems. Targeted arterial delivery of 12-MTA resulted in dose-dependent growth inhibition of intramuscular rabbit VX2 tumors while myristic acid, a saturated fatty acid of the same carbon length as 12-MTA, was found to stimulate tumor growth. Two and 7 days following treatment, tumors treated with 12-MTA showed a significant decrease in 5-hydroxyeicosatetraenoic acid (5-HETE) and a concomitant increase in 15-HETE levels while tumors treated with myristic acid exhibited a significant increase in prostaglandin E2 (PGE2) levels. Western blot as well as immunohistochemical analysis showed that 5-LOX and COX-2 proteins were present in the VX2 tumors. No alterations in tumor/tumor cell morphology or caspase-3 activity were evident on microscopic examination following treatment. These studies suggest that targeted arterial delivery of branched chain fatty acids such as 12-MTA may be considered as a potential new therapy for treatment of solid tumors. The exact mechanism(s) responsible for the observed inhibition of VX2 tumor growth by 12-MTA is unclear. Additional in vivo studies are warranted to elucidate 12-MTA's mechanism of action and further investigate the branched chain fatty acid's antitumor effects.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1989

Radioiodinated fatty acid esters in the management of hepatocellular carcinoma: preliminary findings.

Radioiodinated fatty acid esters, such as lipiodol or ethiodol, are localized in the hypervascular hepatocellular carcinoma (HCC) for a long time following intra-arterial hepatic injection, enabling delivery of high internal radiation to the tumor. The desired radiation can easily be delivered to small HCC, less than 5 cm in diameter, in single or multiple procedures with an 8-week interval. For larger tumors, [131I]lipiodol or [131I]ethiodol in conjunction with chemotherapy emulsion, Ivalon embolization or all three combinations should be considered for maximal clinical results. A strong beta emitter with shorter physical half-life, i.e. 90Y will be more effective in the management of HCC if one can label lipiodol with 90Y.

Adult↗
PubMed1995

Treatment of hepatic-metastatic colorectal cancer with a chemotherapeutic emulsion: interim results of a phase I trial.

BACKGROUND: Hepatic arterial infusion of 5-fluoro-2-deoxyuridine (FUdR) is associated with a 60% response rate among previously untreated patients who have hepatic-metastatic colorectal cancer. One obstacle to further dose escalation has been concomitant hepatic toxicity. We are evaluating a FUdR-containing chemotherapeutic emulsion to further dose intensify therapy without associated toxicity. METHODS: The in vitro pharmacokinetics of the emulsion were determined using high-pressure liquid chromatography (HPLC). The rate at which FUdR is released from emulsion into an overlying aqueous phase was determined in static and dynamic assays. Fifteen patients with hepatic-metastatic colorectal cancer were treated with intrahepatic arterial infusions of emulsion on a phase I dose-escalating clinical protocol. Serum collection determined systemic drug levels using HPLC. RESULTS: In vitro studies demonstrate that FUdR is slowly released from emulsion into overlying aqueous medium. The emulsion serves as a depot for FUdR. Therapy was well tolerated. Emulsion was sequestered in the liver after infusion in all treated patients. CONCLUSIONS: This Ethiodol-based, oil-in-water emulsion serves as a sustained-release preparation of FUdR. An Ethiodol-based oil-in-water emulsion is a clinically effective vehicle for delivering FUdR to hepatic-metastatic colorectal tumors.

Aged↗
PubMed2005

Hepatic arterial chemoembolization for hepatocellular carcinoma: comparison of survival rates with different embolic agents.

PURPOSE: The optimal embolic agent for transhepatic arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) has not been identified. This study reports outcomes of TACE for HCC with Gelfoam powder and polyvinyl alcohol (PVA). MATERIALS AND METHODS: Eighty-one patients underwent 152 TACE sessions with Gelfoam powder (n = 41) or polyvinyl alcohol (PVA) and Ethiodol (n = 40) as the embolic agent. Chemotherapeutic drugs were the same for all patients (50 mg cisplatin, 20 mg doxorubicin, 10 mg mitomycin-c). The groups were compared based on number of TACE sessions, maximum tumor size, bilirubin level, aspartate and alanine aminotransferase levels, Child-Pugh score, Model for End-stage Liver Disease score, and hepatitis B or C virus positivity. The number of cases of each Child class in each group was also evaluated. Survival starting from the first TACE session was calculated according to Kaplan-Meier analysis. Forty-eight patients died during the study period, 19 received transplants, and 14 were alive at the end of the study period. RESULTS: The groups were statistically similar in all categories regarding liver function, Child-Pugh score, tumor size, hepatitis status, and percentage of patients with Child class A, B, and C disease. The number of TACE sessions was significantly greater for the Gelfoam powder group (mean, 2.2) versus the PVA group (mean, 1.6; P = .01). Overall survival was similar between groups whether patients who received transplants were included in the analysis (mean, 659 days +/- 83 with Gelfoam powder vs 565 days +/- 71 with PVA; P = .42) or were excluded (mean, 519 days +/- 80 with Gelfoam powder vs 511 days +/- 75 with PVA; P = .93). CONCLUSION: In similar patient groups, survival after treatment of HCC with TACE with Gelfoam powder or PVA and Ethiodol was similar.

Antineoplastic Agents↗
PubMed1980

Dermatitis associated with Evans blue dye.

A 73-year-old woman developed an allergic contact dermatitis of the feet and legs 24 days following lymphangiography. Dermatitis was accompanied by a generalized urticarial reaction. Intracutaneous skin testing was positive to Evans blue dye, used as a lymphatic marker, but negative to Ethiodol, an iodine-containing contrast medium. Soft tissue x-rays x-rays revealed extravasated Ethiodol in the left leg but not in the right, while dermatitis occurred on both legs. This finding, combined with the positive skin test to Evans blue, stress the importance of testing with both agents when dermatitis develops following lymphangiography. Intracutaneous rather than epicutaneous testing is the indicated route and may be related to the route of sensitization.

Aged↗