Chronic toxicity study in dogs following intralymphatic injections of ethiodol, ethiodol with chlorophyll and sterile non-iodinized poppy seed oil.
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Animals↗
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Ethiodol oil contrast medium inhibits macrophage phagocytosis and adherence by altering membrane electronegativity and microviscosity.
OBJECTIVE: To examine the effect of Ethiodol oil-soluble contrast medium and Sinografin aqueous-soluble contrast medium on macrophage function. After the observation that Ethiodol alters macrophage phagocytosis and adherence, we sought to determine the mechanism of action by which oil-soluble contrast medium alters the macrophage membrane. DESIGN: The P388D1 cell line was used as a consistent source of macrophages for all experiments. The uptake of 3H-labeled candida albicans was determined in macrophages exposed to 1:100, 1:400, or 1:800 dilutions of Ethiodol, Sinografin (S.R. Squibb, Princeton, NJ) or untreated media. To evaluate the macrophage adherence, 51Cr-labeled macrophages were exposed to the same dilutions of the contrast media. Specific membrane properties, Fc receptor levels, electronegativity, and microviscosity were assessed by flow cytometry after exposure to 1:100 dilutions of Ethiodol or Sinografin. RESULTS: Macrophage phagocytosis was decreased upon exposure to 1:100 and 1:400 dilutions of Ethiodol contrast medium, whereas adherence was reduced at the 1:100 dilution of Ethiodol. There was no effect of any dilution of Sinografin. There was a reduction in membrane electronegativity and microviscosity, but not Fc receptor levels, after exposure to a 1:100 dilution of Ethiodol. CONCLUSIONS: This study establishes a decrease in macrophage phagocytosis and adherence after exposure to Ethiodol oil-soluble contrast medium. We established that this alteration in membrane function is caused by a reduction of membrane negative surface charge and microviscosity. This may suggest a mechanism of action for the therapeutic effect of oil-contrast hysterosalpingograms in women with unexplained infertility.
Animals↗
Evaluation of intrahepatic I-131 ethiodol on a patient with hepatocellular carcinoma. Therapeutic feasibility study.
This study assesses the therapeutic efficacy of radiolabeled iodized oil on a patient with hepatocellular carcinoma (HCC). An iodized oil, such as Lipiodol or Ethiodol (Savage Laboratories, Melville, NY), was retained selectively in the tumor vessels of large tumors as well as in the daughter tumors of HCC for long periods of time following intra-arterial injection into the hepatic artery proper. A small fraction of the stable iodine (1 pg of I-127) of the 37% iodine by weight in Ethiodol was replaced by the I-131 with 100% efficiency. A patient with HCC was injected with I-131 Ethiodol into the hepatic artery. Sequential imaging of organs such as the liver, lung, stomach, and thyroid over an eight-day period demonstrated a high tumor-to-normal-liver ratio and a negligible amount of radioactivity in these organs. These findings indicate that I-131 Ethiodol, or Ethiodol labeled with other pure beta emitters, such as Y-90 or P-32, will be effective delivering a high internal radiation dose to HCC with a small radiation effect to normal tissues. To evaluate its potential as a radiotherapeutic agent for HCC, the kinetics, biodistribution, determination of absolute activity in the tumor following intra-arterial injection of I-131 Ethiodol will be studied in the future. At the same time, an effort will be made to label Ethiodol with Y-90 and P-32.
Angiography↗
A novel approach to flow quantification in brain arteriovenous malformations prior to enbucrilate embolization: use of insoluble contrast (Ethiodol droplet) angiography.
OBJECT: Successful therapeutic embolization of arteriovenous malformations (AVMs) of the brain with liquid polymers (glues) requires precise knowledge of highly variable AVM structure and flow velocities and transit times of blood through the AVM nidus. The goal of this study was to improve AVM flow measurement and visualization by the substitution of the insoluble Ethiodol (ethiodized oil) contrast agent for the soluble contrast media normally used in angiographic studies. METHODS: Before enbucrilate embolization of 24 AVM feeding pedicles in 13 patients, standard contrast medium was superselectively injected into each target pedicle, followed by infusion of 20 microl of Ethiodol microdroplets. Transport of contrast material was assessed using high-speed biplane pulsed digital subtraction angiography (DSA) operating at 15 frames per second. The mean blood flow transit times through AVMs after administration of Ethiodol were found to be approximately half as long as in those measured after injection of soluble contrast materials (0.22 +/- 0.10 seconds compared with 0.46 +/- 0.19 seconds [mean +/- standard deviation]; p < 0.0001). The discrete Ethiodol microdroplets travel with the core flow, more closely approximating the dynamic behavior of enbucrilate, allowing the AVM structure to be traced with high spatial and temporal resolution. There were no inadvertent vessel occlusions or pulmonary complications related to the use of Ethiodol for DSA. CONCLUSIONS: Because of diffusion and convection, forces that decrease concentration, visualization of the contrast front is reduced, often resulting in deceptively long transit times when soluble contrast materials are used. Overestimation may prove dangerous when planning embolizations. The Ethiodol droplet DSA method provides accurate transit time measurements and precise, detailed, and dynamic AVM visualization. Further development of this method will improve the safety and precision of AVM treatments.
Adolescent↗
Hepatography and liver lymphography by retrograde biliary ethiodol infusion: an experimental study in the dog.
Ethiodol in dosages of 0.5-3 ml/kg was retrogradely infused with hydrostatic pressure of 50--100 cm water into the biliary system of nine cholecystectomized dogs equipped with a Thomas cannula in the second portion of the duodenum, allowing cannulation of the common bile duct with a Foley catheter under direct vision. A total of 18 examinations were performed. A dense hepatogram and complete visualization of the hepatic lymph nodes were obtained when the infused Ethiodol dosage exceeded the capacity of the biliary system by 10 ml or more. The hepatogram lasted for three to four months and the lymph nodes were opacified for a year and longer. Contrary to angiographic contrast agents, Ethiodol retrogradely infused into the biliary system primarily refluxes from the biliary system to the lymph and not to the blood. Judged by serial chest radiographs and lung scans, pulmonary Ethiodol emboli did not occur. A significant temporary increase in serum bilirubin and liver enzymes followed the procedure but these returned to normal within a week to a month. Periodic needle biopsies of the liver showed Ethiodol droplets initially in the interstitium and lymphatics, and subsequently in hepatocytes, Kupffer's cells and the epithelium of small bile ductules. No hepatic damage was found histologically on long-time follow-up examinations.
Animals↗
Comparison of radiopaque perfluorocarbon and Ethiodol in lymphography.
Lymphangiography was performed on 40 adult cats, 39 dogs, 20 rabbits, and 12 rats of mixed sex using Ethiodol or radiopaque perfluorocarbon (BPC). Ethiodol was more radiodense than RPC, but imaging of lymph channels and nodes was satisfactory with the latter. RPC could be infused rapidly, while Ethiodol infusion was time consuming. RPC was biologically inert; Ethiodol produced both local and systemic inflammatory reactions. The lymph node distribution with RPC was more uniform and persisted for longer periods. It was concluded that RPC was an improvement over Ethiodol for lymphangiography.
Animals↗
Ether-dissolved ethiodol for lymphangiography: an experimental study.
In order to decrease administration time, the viscosity of Ethiodol was reduced by mixing it with ether; this mixture was evaluated in lymphangiography of dogs. The ether-Ethiodol solution was injected into a cannulated lymph vessel of one hind limb and compared to pure Ethiodol in the other. For the ether-Ethiodol solution, the time required for complete injection was 10-30 min in most cases compared to 60-105 min for Ethiodol alone. The radiographic appearance of the lymph vessels and nodes appeared similar on both sides, and follow-up lymphangiograms in two animals after 1 and 3 weeks showed no difference from the original study. Microscopic examination of the opacified lymph nodes on both sides revealed no histologic differences. The techniques has potential clinical application.
Animals↗
Experimental evaluation of ethanol-ethiodol for transcatheter renal embolization.
Adult mongrel dogs were used to evaluate and compare the use of ethanol and ethanol-Ethiodol for transcatheter renal arterial embolization. Each agent was administered into a main renal artery in five dogs and evaluated with regard to ease of use, radiopacity, arterial occlusion, parenchymal damage, and toxicity. Both agents were easy to inject, and no complications were encountered in any of the animals. Ethiodol added the ability to fluoroscopically monitor the infusate for reflux and distribution, yielded a more homogeneous distribution of the ethanol within the renal vasculature, and increased the embolic effects of the ethanol. Adding Ethiodol to ethanol should decrease the latter's complications since administration can be monitored fluoroscopically and a smaller volume of ethanol could perhaps be used to achieve the desired result. Additional research is needed to determine the safety of administering larger volumes of Ethiodol into the renal artery.
Animals↗
90Y-oxine-ethiodol, a potential radiopharmaceutical for the treatment of liver cancer.
Ethiodol (or lipiodol) is selectively retained in hepatocellular carcinoma and is used as a vehicle to deliver radioactive agents following intraarterial hepatic infusion. We prepared the lipophilic complex 90Y-oxine with a radiolabeling efficiency of 97.6+/-1.1%. After extraction into ethiodol, a stability test in serum at 37 degrees C showed that 87.8% of the 90Y remained ethiodol-bound for 7 days. Bremsstrahlung imaging of a rabbit for 48 h confirmed that the homogeneous mixture of radiolabeled 90Y-oxine and ethiodol stayed in the targeted liver lobe. This radiopharmaceutical is thus a potential candidate for the treatment of non-resectable liver cancer.
Angiography↗
Dosimetry of iodine-131 ethiodol in the treatment of hepatoma.
The in vivo distribution and kinetics of [131I]Ethiodol injected through the hepatic artery have been measured on a group of four patients with hepatocellular carcinoma. The [131I]Ethiodol was distributed predominantly in the liver (70-90%) and lungs (10-20%) and was selectively concentrated and retained in the patients with massive and multinodular hepatomas with approximately 10% of the administered activity localizing in tumor. The radioactivity in the blood 2 hr postinjection was less than 0.1% and was never higher than 0.9% of the administered activity. The radioactivity cleared from normal liver tissue with an effective half-life of approximately 4 days while the clearance time from the tumor was 20-25% longer. Activity in the lungs initially increased and then cleared with a 5-day effective half-life. Based on these measurements, the estimated dose per mCi of [131I]Ethiodol administered is 31 rad to the liver, 22 rad to the lungs, 1.9 rad to the total body and 239 rad to a 4-cm diameter tumor. These results suggest that [131I]Ethiodol has the potential to deliver curative radiation doses to hepatomas with acceptable radiation burdens to normal tissues.
Adult↗
Efficacy and safety of preoperative lobar or segmental ablation via transarterial administration of ethiodol and ethanol mixture for treatment of hepatocellular carcinoma: clinical study.
Transarterial embolization (TAE) using various thrombotic substances for unresectable hepatocellular carcinoma (HCC) performed on many patients has resulted in a better survival rate. We evaluated the efficacy and clinical safety of using an Ethiodol-ethanol mixture as the embolizer for treatment of HCC and the possibility of a surgical approach for inoperable tumors after TAE. Twenty patients with HCC who underwent TAE and tumor resection were included in the study. Initially, eight had increased retention rate of indocyanine green dye via intravenous injection (0.5 mg/kg) at 15 minutes (ICGR15), and six had an insufficient residual volume that precluded them from undergoing tumor resection. TAE was performed by slowly infusing the mixture of Ethiodol and ethanol into the artery supplying the tumor until dual hepatic artery and portal vein embolization was achieved. Serum levels of alanine aminotransferase increased after embolization, but all biochemistry studies reverted to normal within 2 weeks. A decreased tumor size (n = 15), improved ICG (n = 8), and increased volume of the nonembolized lobe (n = 10) were noted. The operations performed were right lobectomy (n = 11), extended right lobectomy (n = 3), left lobectomy (n = 2), extended left lobectomy (n = 2), and wedge resection (n = 2), which included patients who did not want to undergo major hepatectomy. Complete tumor necrosis was found in seven cases. All patients survived with no associated complications. The 1-year survival rate was 95%. Transarterial Ethiodol and ethanol administration creating dual hepatic artery and portal vein embolization was a safe and efficacious method for treating HCC. It effectively decreases tumor size, causes compensatory hepatic hypertrophy, and improves the ICGR15, which allows a wider range of patients to undergo liver surgery and achieve better survival.
Adult↗
Evaluation of perfluoroctylbromide for lymphography in the dog: comparison with ethiodol.
The efficacy and safety of perfluoroctylbromide as a diagnostic contrast agent for direct lymphography was studied in mongrel dogs. This radiopaque perfluorocarbon has several advantages over Ethiodol. The liquid compound has injection times one-fifth of that required for Ethiodol. When dosages were three to four times that necessary for radiograms, the lungs of perfluoroctylbromide dogs tolerated the increase better than the Ethiodol dogs. Although the radiopacity is less, radiographs were acceptable. The less radiopacity of the fluoroctylbromide nodes may be of greater significance in the larger body of the human.
Animals↗
Sarcomas metastatic to the liver: response and survival after cisplatin, doxorubicin, mitomycin-C, Ethiodol, and polyvinyl alcohol chemoembolization.
PURPOSE: To evaluate the response to and survival after chemoembolization with cisplatin, doxorubicin, mitomycin-C, Ethiodol, and polyvinyl alcohol for patients with sarcomas metastatic to the liver that are surgically unresectable. MATERIALS AND METHODS: Sixteen patients were treated. Primary tumors included 11 gastrointestinal leiomyosarcomas, two splenic angiosarcomas, one leiomyosarcoma of the broad ligament, one leiomyosarcoma of the inferior vena cava, and one malignant fibrous histiocytoma of the colon. Chemoembolization with cisplatin, doxorubicin, mitomycin-C, Ethiodol, and polyvinyl alcohol particles was performed 1-5 times at approximately monthly intervals (mean, 2.8). Pre- and posttreatment cross-sectional imaging was performed 1 month after completion of treatment and then every 3 months. Thirty-day response was graded according to World Health Organization/Eastern Cooperative Oncology Group criteria. Survival was calculated with use of Kaplan-Meier analysis. RESULTS: Two patients (13%) exhibited partial morphologic response, 11 patients (69%) were morphologically stable, and three (19%) demonstrated progression of disease 30 days after completion of treatment. Among the 13 responders, two underwent partial hepatectomy after initial treatment. Seven developed intrahepatic progression at a mean of 10 months and a median time of 8 months. The remaining four patients had no documented intrahepatic progression at the time of last imaging follow-up. Nine patients developed extrahepatic progression at a mean time of 6.3 months and a median time of 6 months, of whom four underwent additional surgical resection. Response to therapy was based on time of first intervention. Cumulative survival from time of diagnosis with use of Kaplan-Meier analysis was 81% at 1 year, 54% at 2 years, and 40% at 3 years. Median survival time was 20 months. Cumulative survival from initial chemoembolization was 67% at 1 year, 50% at 2 years, and 40% at 3 years, with a median survival time of 13 months. The thirty-day mortality rate was zero. CONCLUSION: Durable tumor response with chemoembolization is possible in this form of metastatic disease, which is highly resistant to systemic chemotherapy.
Chemoembolization, Therapeutic↗
Effects of a mixture of a low concentration of n-butylcyanoacrylate and ethiodol on tissue reactions and the permanence of arterial occlusion after embolization.
OBJECTIVE: Cyanoacrylates are the most commonly used liquid embolic agents. For embolization of arteriovenous malformations, a mixture of a low concentration of n-butylcyanoacrylate (NBCA) and Ethiodol (Savage Laboratories, Melville, NY) has been recommended for deeper penetration of the nidus. Dilution of NBCA, however, might result in different degrees of tissue reaction and might influence the permanence of vessel occlusion, with an increased risk of vessel recanalization. We compared tissue reactions induced by different NBCA/Ethiodol mixtures and analyzed the permanence of their embolic effects. METHODS: NBCA was diluted with Ethiodol to prepare the following standard solutions: Mixture A, low concentration (NBCA/Ethiodol ratio of 20:80); Mixture B, high concentration (50:50). The study was designed in two parts, because tissue reactions after embolization are considered to be a combination of foreign body reactions to solidified material and reactions to the injured blood vessel. Foreign body reactions were studied by intramuscularly injecting both glue mixtures into the backs of 18 rats. Specimens were obtained at various times after implantation. Immunohistochemical analysis and esterase staining were used to detect macrophages and neutrophils, respectively. The densities of these inflammatory cells were calculated and statistically compared. To study the degree of vascular wall injury and the permanence of embolic effects, the renal arteries in 48 rabbits were embolized with NBCA Mixture A or B. Six specimens for each group were obtained at various times after embolization. RESULTS: There was no significant difference in foreign body reactions between groups treated with Mixtures A and B, at any time. However, the macrophage density was larger for both groups at 3 months versus 3 days and for the group treated with Mixture B at 3 months versus 2 weeks. There was no difference in the degree of vessel wall injury. None of the embolized vessels demonstrated evidence of recanalization. CONCLUSION: The low concentration of NBCA induced a tissue response similar to that of the high-concentration form. Embolized vessels exhibited no greater incidence of recanalization. Therefore, embolization of arteriovenous malformations with diluted NBCA may be safe.
Animals↗
Chemoembolization of hepatocellular carcinoma with cisplatin, doxorubicin, mitomycin-C, ethiodol, and polyvinyl alcohol: prospective evaluation of response and survival in a U.S. population.
PURPOSE: To evaluate response and survival after hepatic chemoembolization with cisplatin, doxorubicin, mitomycin-C, Ethiodol, and polyvinyl alcohol in a U.S. population of patients with hepatocellular carcinoma. MATERIALS AND METHODS: Thirty-eight consecutive patients were treated: 35% stage I, 62% stage II, 3% stage III. Fifty-one percent had cirrhosis. Chemoembolization was performed at approximately monthly intervals for one to seven sessions (mean, 2.2). Pretreatment and posttreatment cross-sectional imaging and alpha-fetoprotein (AFP) levels were obtained prospectively 1 month after treatment and then every 3 months. Thirty-day response was calculated by means of the the World Health Organization/Eastern Cooperative Oncology Group criteria. RESULTS: One patient was lost to follow-up. In seven patients, lesions became resectable after chemoembolization. Among 13 evaluable patients with initially elevated AFP level, 70% had a partial biologic response (>50% decrease in AFP), 15% had a minor response (25-50% decrease), and the remaining 15% remained stable. Among 25 patients evaluable for morphologic response, 36% had a partial response, 32% had a minor response, and 32% remained stable. No patients had progression of disease while receiving therapy. The cumulative survival was 60% at 1 year, 41% at 2 years, and 16% at 3 years. Two patients developed progressive hepatic failure. Thirty-day mortality was 3% (one patient). CONCLUSION: These results compare favorably to published response and survival data for chemoembolization of advanced hepatocellular carcinoma from Asia and Europe.
Antibiotics, Antineoplastic↗
Capillary embolization using ethiodol-ethanol for complete renal ablation in Swine.
RATIONALE AND OBJECTIVES: To evaluate the effect of capillary embolization with superselectively administered 1:1 Ethiodol-ethanol mixture (EEM) for complete nephrectomy in normal porcine kidneys. MATERIALS AND METHODS: One kidney in each animal was completely embolized by sequential segmental arterial injections of the EEM via a microcatheter until complete capillary stasis occurred. Group 1 (n = 5): Initial embolization did not occlude the arterial compartment. Group 2 (n = 7): The capillary embolization was performed in conjunction with absolute ethanol injection and coil placement during balloon catheter occlusion. RESULTS: Group 1: Complete recanalization occurred following the EEM embolization (1-week). After the repeat embolization (EEM + pure ethanol without balloon occlusion), three of five kidneys showed partial recanalization (2-weeks). Following a third embolization (EEM + coil) in two pigs, one kidney showed partial recanalization (12-weeks). Group 2: Complete renal artery occlusion was achieved in all kidneys with no recanalization. Histologically, four kidneys exhibited total ablation whereas three showed minimal preexisting parenchyma (8-weeks). CONCLUSIONS: Permanent arterial occlusion with histologically complete renal ablation was achieved using a two-phase technique of homogeneous capillary embolization with 1:1 EEM and ethanol and coil occlusion performed during temporary balloon occlusion. Sequential segmental EEM injections alone did not produce permanent capillary embolization.
Animals↗
Renal cisplatin chemoembolization with Angiostat, Gelfoam, and Ethiodol in the rabbit: renal platinum distributions.
Renal platinum distributions were determined in rabbits after administration of 0.4 mL of 1 mg/mL cisplatin by intravenous infusion, by injections into the left renal artery with aqueous contrast material and with lipid contrast material (Ethiodol), and by chemoembolization of the left renal artery with concurrent administration of various concentrations of two collagen carriers, Angiostat collagen for embolization and Gelfoam gelatin. Renal platinum concentration was measured in tissue homogenates at 2 1/2 hours with atomic absorption spectrometry. Target-kidney platinum levels were 5.4 and 6.9 times the contralateral-kidney levels after intraarterial infusion of aqueous and lipid contrast media, respectively. With Angiostat and Gelfoam chemoembolization, renal platinum retention and collagen concentration were linearly related (r = .87 and .81, P less than .001). Target-kidney-contralateral-kidney platinum ratios were 57:1 for 30 mg/mL Gelfoam and 220:1 for 10 mg/mL Angiostat. The difference in regional drug retention for Angiostat versus Gelfoam reflects the stable fiber integrity of Angiostat.
Animals↗
Pitfalls to avoid: accidental intravenous injection of Ethiodol.
Direct intravenous injection of Ethiodol occurred at lymphography. Early fluoroscopic or radiographic film evaluation, and careful monitoring of injection rates, would help to avoid this complication.
Ethiodized Oil↗