Lipiodol

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Iodized oil
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Trade names Lipiodol, Ethiodol, Vividol
Other namesethiodized oil, ethyl esters of iodised fatty acids
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administration 		by mouth, injection (IM, intralymphatic, intrauterine, selective hepatic intra-arterial)
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Iodized oil, also known as ethiodized oil, brand name Lipiodol, is a medication derived from poppyseed oil and iodine. When given by injection, it is a radio-opaque contrast agent that is used to outline structures in radiological investigations. [2] [3] When given orally or by intramuscular injection once or twice a year, it prevents endemic goitre in remote communities. [4] It has an additional use in gastric variceal obliteration as a dilutant that does not affect polymerization of cyanoacrylate.

Contents

When used as tissue contrast, iodized oil has a risk of entering the vein and causing embolism in the brain and lungs. [5] There is a boxed warning referring to the risk of embolism. [6] Use as iodine supplementation is recommended in regions where deficiency is common, otherwise it is not recommended. [4] It should not be used for hysterosalpingography in pregnancy. [6]

Iodized oil was first made in 1901 by Marcel Guerbet and Laurent Lafay. Originally used to treat iodine deficiency, it was identified as an effective radiocontrast in 1921 by Sicard and Forestier, before returning as a tool to treat iodine deficiency in goiter eradication campaigns of the 1980s. [7] Under the name "iodine", iodized oil is on the World Health Organization's List of Essential Medicines, in liquid and capsule form. [4] [8]

Medical uses

Imaging

Iodized oil is a radio-opaque contrast agent. It is used in chemoembolization applications as a contrast agent in follow-up imaging. [9] Lipiodol is also used in lymphangiography, the imaging of the lymphatic system. [10]

Historically Lipiodol was often used as a contrast medium at hysterosalpingography (HSG: a procedure to determine tubal patency [i.e. whether the fallopian tubes are open], used in the investigation of subfertility). It became less commonly utilized in the 1960s to 1980s because the more modern water-soluble media give images that are easier to interpret. There is also an important safety issue with Lipiodol in that intravasation (leakage) of the fluid into the venous system has caused complications in the past. [11]

Chemoembolization

Lipiodol is used in conventional transcatheter arterial chemoembolization (TACE), a procedure for treating liver tumors. An anticancer drug is first emulsified into lipiodol to form a suspension. Guided by an imaging system, a catheter is moved into an artery that feeds the tumor and injects the suspension. Lipiodol helps retain the drug around the cancer cells. An embolic material is then injected to restrict blood supply to the tumor. [12]

"Transarterial radioembolization" (TARE) is a similar procedure where the anticancer drug is radioactive. An experimental version of TARE uses iodine-131-labeled lipiodol. The radioactive lipiodol is attracted to the tumor, much like regular lipiodol. Its radioactivity destroys tumor tissue. [13] However, I131-lipiodol has been withdrawn from the market by its European manufacturer due to risk of embolism, especially in patients with hepatic arterio-venous shunting. [14] I131-lipidol is also less tumor-targeted than the microbeads used in conventional TARE procedures, requiring much higher radiation doses. [15] It remains available in India, where its cost-effectiveness over conventional Y90 TARE is valued. [16]

Gastric variceal obliteration

It has an additional use in gastric variceal obliteration as a dilutant that does not affect polymerization of cyanoacrylate.

Fallopian tube flushing

Since the 2000s, a small number of studies have suggested that flushing lipiodol through the fallopian tubes (similar to what is done in HSG, but without imaging) might provide a short-term rise in fecundity in patients with unexplained infertility. This procedure is called Lipiodol flushing or more broadly tubal flushing. A 2005 systematic review has suggested a significant increase in fertility, especially in those women who have endometriosis when using Lipiodol flushing. [11] A 2020 Cochrane review suggests that flushing with oil-soluble contrast media such as lipiodol may increase the chance of live birth and clinical pregnancy. [17]

Iodine deficiency

Lipiodol is given once or twice yearly to remote communities at risk of endemic goitre. [4] The oil can be taken orally or injected intermuscularly. There is also an oral capsule that contains the oil, equivalent to 190 mg iodine. [18] [19]

Iodized poppyseed oil (Lipiodol) given orally or intermuscularly produces a long-lasting store of iodine in the body, allowing very infrequent dosing. Iodized oil is a cost-effective way of combating iodine deficiency. There seems to be a lower risk of initial hyperthyroidism compared to iodized salt. [20] Beyond poppyseed oil, locally-available rapeseed (Brassiodol), peanut, walnut, and soybean oils [21] have also been used for producing iodized oil for oral use. These iodized oils have different pharmacological profiles, but have also proven successful in eradicating goiter at a lower cost. [20] In fact, iodized rapeseed and peanut oils provide longer-lasting protection from goiter compared to Lipiodol. [22] [23]

Chemistry

Ethiodized oil is composed of iodine reacted with ethyl esters of fatty acids of poppyseed oil, primarily as ethyl monoiodostearate and ethyl diiodostearate. One method to produce the oil involves turning iodine into anhydrous hydroiodic acid using silylated reagents, then reacting the acid with fatty acid ethyl esters. Sufficient amounts of the acid is used to ensure that all double bonds are iodinated. The product is washed and purified to remove any free elemental iodine and other organic compounds, leaving only the iodinated esters. [22]

History

Lipiodol was first synthesized by Marcel Guerbet in the Paris School of Pharmacy in 1901. It was originally used to treat iodine deficiency. [7]

Historically, Lipiodol was the first iodinated contrast agent (used for myelography by two French physicians, Jacques Forestier and Jean Sicard in 1921). [7] It was first used for lymphography in 1960 as a replacement for the earlier water-soluble contrasts, which quickly diffused outside the lymphatic network and prevented visualization beyond the first few nodes. A transesterified version, Lipiodol Ultra Fluide, was proposed by Wallace specifically for this purpose in 1960. [7] : 168  In 1981, Japanese professor Konno found that when Lipidol is injected into the hepatic artery of patients with hepatocarcinoma, the oily substance is selectively retained by the tumor for several months. He mixed Lipidol with a new drug SMANCS to selectively target cancer cells; thus, chemoembolization was born. [7] : 168 

The use of Lipiodol against iodine deficiency was revived in 1957 by Mac Cullagh, who used it in Papua New Guinea to fight endemic goitre via intramuscular injection. The technique received increasing approval and refinement as a supplement to salt iodization from the Pan American Health Organisation, UNICEF, and WHO. In 1989, it was added to the WHO Model List of Essential Medications. [7] : 169 

Supply status

Savage Laboratories supplied thiodized oil for interventional procedure under the brand name "Ethiodol" to the US market until 2011, when the product was discotinued. The Ethiodol product is equivalent to Lipiodol Ultra Fluide. [24]

Ethiodized oil for interventional procedure was solely produced and marketed by Guerbet, until Vivere Imaging launched its oil under the brand name "Vividol" in 2022.

Related Research Articles

<span class="mw-page-title-main">Congenital iodine deficiency syndrome</span> Impaired physical and mental development due to insufficient iodine intake

Congenital iodine deficiency syndrome (CIDS) is a medical condition present at birth marked by impaired physical and mental development, due to insufficient thyroid hormone (hypothyroidism) often caused by insufficient dietary iodine during pregnancy. It is one cause of underactive thyroid function at birth, called congenital hypothyroidism, historically referred to as cretinism (obsolete). If untreated, it results in impairment of both physical and mental development. Symptoms may include goiter, poor length growth in infants, reduced adult stature, thickened skin, hair loss, enlarged tongue, a protruding abdomen; delayed bone maturation and puberty in children; and mental deterioration, neurological impairment, impeded ovulation, and infertility in adults.

<span class="mw-page-title-main">Goitre</span> Neck swelling due to enlarged thyroid gland

A goitre, or goiter, is a swelling in the neck resulting from an enlarged thyroid gland. A goitre can be associated with a thyroid that is not functioning properly.

<span class="mw-page-title-main">Hepatocellular carcinoma</span> Medical condition

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and is currently the most common cause of death in people with cirrhosis. HCC is the third leading cause of cancer-related deaths worldwide.

Liver tumors are abnormal growth of liver cells on or in the liver. Several distinct types of tumors can develop in the liver because the liver is made up of various cell types. Liver tumors can be classified as benign (non-cancerous) or malignant (cancerous) growths. They may be discovered on medical imaging, and the diagnosis is often confirmed with liver biopsy. Signs and symptoms of liver masses vary from being asymptomatic to patients presenting with an abdominal mass, hepatomegaly, abdominal pain, jaundice, or some other liver dysfunction. Treatment varies and is highly specific to the type of liver tumor.

Radiocontrast agents are substances used to enhance the visibility of internal structures in X-ray-based imaging techniques such as computed tomography, projectional radiography, and fluoroscopy. Radiocontrast agents are typically iodine, or more rarely barium sulfate. The contrast agents absorb external X-rays, resulting in decreased exposure on the X-ray detector. This is different from radiopharmaceuticals used in nuclear medicine which emit radiation.

Poppyseed oil is an edible oil obtained from poppy seeds.

<span class="mw-page-title-main">Iodised salt</span> Table salt preparation with iodide salts added

Iodised salt is table salt mixed with a minute amount of various salts of the element iodine. The ingestion of iodine prevents iodine deficiency. Worldwide, iodine deficiency affects about two billion people and is the leading preventable cause of intellectual and developmental disabilities. Deficiency also causes thyroid gland problems, including endemic goitre. In many countries, iodine deficiency is a major public health problem that can be cheaply addressed by purposely adding small amounts of iodine to the sodium chloride salt.

<span class="mw-page-title-main">Embolization</span> Passage and lodging of an embolus within the bloodstream

Embolization refers to the passage and lodging of an embolus within the bloodstream. It may be of natural origin (pathological), in which sense it is also called embolism, for example a pulmonary embolism; or it may be artificially induced (therapeutic), as a hemostatic treatment for bleeding or as a treatment for some types of cancer by deliberately blocking blood vessels to starve the tumor cells.

Transcatheter arterial chemoembolization (TACE) is a minimally invasive procedure performed in interventional radiology to restrict a tumor's blood supply. Small embolic particles coated with chemotherapeutic drugs are injected selectively through a catheter into an artery directly supplying the tumor. These particles both block the blood supply and induce cytotoxicity, attacking the tumor in several ways.

Iodine deficiency is a lack of the trace element iodine, an essential nutrient in the diet. It may result in metabolic problems such as goiter, sometimes as an endemic goiter as well as congenital iodine deficiency syndrome due to untreated congenital hypothyroidism, which results in developmental delays and other health problems. Iodine deficiency is an important global health issue, especially for fertile and pregnant women. It is also a preventable cause of intellectual disability.

The Jod-Basedow effect is hyperthyroidism following administration of iodine or iodide, either as a dietary supplement, for iodinated contrast medical imaging, or as a medication.

<span class="mw-page-title-main">Toxic multinodular goitre</span> Enlarged thyroid gland, causing symptoms of hyperthyroidism

Toxic multinodular goiter (TMNG), also known as multinodular toxic goiter (MNTG), is an active multinodular goiter associated with hyperthyroidism.

Hepatectomy is the surgical resection of the liver. While the term is often employed for the removal of the liver from a liver transplant donor, this article will focus on partial resections of hepatic tissue and hepatoportoenterostomy.

<span class="mw-page-title-main">Hepatocellular adenoma</span> Hepatocellular adenoma (HA) is a rare benign tumor of the liver

Hepatocellular adenoma is a rare, benign liver tumor. It most commonly occurs in people with elevated systemic levels of estrogen, classically in women taking estrogen-containing oral contraceptive medication.

<span class="mw-page-title-main">Liver cancer</span> Medical condition

Liver cancer, also known as hepatic cancer, primary hepatic cancer, or primary hepatic malignancy, is cancer that starts in the liver. Liver cancer can be primary in which the cancer starts in the liver, or it can be liver metastasis, or secondary, in which the cancer spreads from elsewhere in the body to the liver. Liver metastasis is the more common of the two liver cancers. Instances of liver cancer are increasing globally.

<span class="mw-page-title-main">Selective internal radiation therapy</span>

Selective internal radiation therapy (SIRT), also known as transarterial radioembolization (TARE), radioembolization or intra-arterial microbrachytherapy is a form of radionuclide therapy used in interventional radiology to treat cancer. It is generally for selected patients with surgically unresectable cancers, especially hepatocellular carcinoma or metastasis to the liver. The treatment involves injecting tiny microspheres of radioactive material into the arteries that supply the tumor, where the spheres lodge in the small vessels of the tumor. Because this treatment combines radiotherapy with embolization, it is also called radioembolization. The chemotherapeutic analogue is called chemoembolization, of which transcatheter arterial chemoembolization (TACE) is the usual form.

Yttrium-90 is a radioactive isotope of yttrium. Yttrium-90 has found a wide range of uses in radiation therapy to treat some forms of cancer. Along with other isotopes of yttrium, it is sometimes called radioyttrium.

Interventional oncology is a subspecialty field of interventional radiology that deals with the diagnosis and treatment of cancer and cancer-related problems using targeted minimally invasive procedures performed under image guidance. Interventional oncology has developed to a separate pillar of modern oncology and it employs X-ray, ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) to help guide miniaturized instruments to allow targeted and precise treatment of solid tumours located in various organs of the human body, including but not limited to the liver, kidneys, lungs, and bones. Interventional oncology treatments are routinely carried out by interventional radiologists in appropriate settings and facilities.

Iodine is a chemical element with many uses in medicine, depending on the form. Elemental iodine and iodophors are topical antiseptics. Iodine, in non-elemental form, functions as an essential nutrient in human biology. Organic compounds containing iodine are also useful iodinated contrast agents in X-ray imaging.

Transarterial bland embolization is a catheter-based tumor treatment of the liver. In this procedure, embolizing agents can be delivered through the tumor's feeding artery in order to completely occlude the tumor's blood supply. The anti-tumor effects are solely based on tumor ischemia and infarction of tumor tissue, as no chemotherapeutic agents are administered. The rationale for the use of bland embolization for hepatocellular carcinoma (HCC) and/or other hyper-vascular tumors is based on the fact that a normal liver receives a dual blood supply from the hepatic artery (25%) and the portal vein (75%). As the tumor grows, it becomes increasingly dependent on the hepatic artery for blood supply. Once a tumor nodule reaches a diameter of 2 cm or more, most of the blood supply is derived from the hepatic artery. Therefore, bland embolization and transarterial chemoembolization (TACE) consist of the selective angiographic occlusion of the tumor arterial blood supply with a variety of embolizing agents, with or without the precedence of local chemotherapy infusion. The occlusion by embolic particles results in tumor hypoxia and necrosis, without affecting the normal hepatic parenchyma.

References

  1. ↑ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA . Retrieved 22 Oct 2023.
  2. ↑ Ahrar K, Gupta S (January 2003). "Hepatic artery embolization for hepatocellular carcinoma: technique, patient selection, and outcomes". Surgical Oncology Clinics of North America. 12 (1): 105–126. doi:10.1016/s1055-3207(02)00089-3. PMID   12735133.
  3. ↑ Sato T (April 2002). "Locoregional immuno(bio)therapy for liver metastases". Seminars in Oncology. 29 (2): 160–167. doi:10.1053/sonc.2002.31716. PMID   11951214.
  4. 1 2 3 4 World Health Organization (2009). Stuart MC, Kouimtzi M, Hill SR (eds.). WHO Model Formulary 2008. World Health Organization. p. 499. hdl: 10665/44053 . ISBN   9789241547659.
  5. ↑ Gomi T, Hasegawa M (2012). "Radiological contrast agents and radiopharmaceuticals". Side Effects of Drugs Annual. 34: 749–760. doi:10.1016/b978-0-444-59499-0.00046-5. ISBN   978-0-444-59499-0.
  6. 1 2 "DailyMed - LIPIODOL- ethiodized oil injection". dailymed.nlm.nih.gov.
  7. 1 2 3 4 5 6 Bonnemain B, Guerbet M (1995). "Histoire du Lipiodol (1901-1994) ou Comment un médicament peut évoluer avec son temps" [The history of Lipiodol (1901-1994) or How a medication may evolve with the times]. Revue d'Histoire de la Pharmacie (in French). 42 (305): 159–170. doi:10.3406/pharm.1995.4238. PMID   11640460.
  8. ↑ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl: 10665/325771 . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  9. ↑ Guan YS, Hu Y, Liu Y (June 2006). "Multidetector-row computed tomography in the management of hepatocellular carcinoma with transcatheter arterial chemoembolization". Journal of Gastroenterology and Hepatology. 21 (6): 941–946. doi: 10.1111/j.1440-1746.2006.04474.x . PMID   16724976. S2CID   40066693.
  10. ↑ Cabanas RM (2000). "The Concept of the Sentinel Lymph Node". Lymphatic Metastasis and Sentinel Lymphonodectomy. Recent Results in Cancer Research. Vol. 157. pp. 109–20. doi:10.1007/978-3-642-57151-0_9. ISBN   978-3-642-63070-5. PMID   10857165.
  11. 1 2 Johnson NP (2005). "A review of the use of lipiodol flushing for unexplained infertility". Treatments in Endocrinology. 4 (4): 233–243. doi:10.2165/00024677-200504040-00004. PMID   16053340. S2CID   25322807.
  12. ↑ de Baere T, Arai Y, Lencioni R, Geschwind JF, Rilling W, Salem R, et al. (March 2016). "Treatment of Liver Tumors with Lipiodol TACE: Technical Recommendations from Experts Opinion". CardioVascular and Interventional Radiology. 39 (3): 334–343. doi:10.1007/s00270-015-1208-y. PMID   26390875. S2CID   12719852.
  13. ↑ Ahmadzadehfar H, Sabet A, Wilhelm K, Biersack HJ, Risse J (November 2011). "Iodine-131-lipiodol therapy in hepatic tumours". Methods. 55 (3): 246–252. doi:10.1016/j.ymeth.2011.05.003. PMID   21664971.
  14. ↑ Andreana L, Isgrò G, Marelli L, Davies N, Yu D, Navalkissoor S, et al. (October 2012). "Treatment of hepatocellular carcinoma (HCC) by intra-arterial infusion of radio-emitter compounds: trans-arterial radio-embolisation of HCC". Cancer Treatment Reviews. 38 (6): 641–649. doi:10.1016/j.ctrv.2011.11.004. PMID   22169503.
  15. ↑ Qian Y, Liu Q, Li P, Han Y, Zhang J, Xu J, et al. (February 2021). "Highly Tumor-Specific and Long-Acting Iodine-131 Microbeads for Enhanced Treatment of Hepatocellular Carcinoma with Low-Dose Radio-Chemoembolization". ACS Nano. 15 (2): 2933–2946. doi:10.1021/acsnano.0c09122. PMID   33529007. S2CID   231788293.
  16. ↑ Patel A, Subbanna I, Bhargavi V, Swamy S, Kallur KG, Patil S (April 2021). "Transarterial Radioembolization (TARE) with 131 Iodine-Lipiodol for Unresectable Primary Hepatocellular Carcinoma: Experience from a Tertiary Care Center in India". South Asian Journal of Cancer. 10 (2): 81–86. doi:10.1055/s-0041-1731600. PMC   8460342 . PMID   34568220.
  17. ↑ Wang R, Watson A, Johnson N, Cheung K, Fitzgerald C, Mol BW, et al. (October 2020). "Tubal flushing for subfertility". The Cochrane Database of Systematic Reviews. 2020 (10): CD003718. doi:10.1002/14651858.CD003718.pub5. PMC   9508794 . PMID   33053612.
  18. ↑ "IODIZED OIL oral | MSF Medical Guidelines". medicalguidelines.msf.org.
  19. ↑ Markou KB, Georgopoulos NA, Makri M, Vlasopoulou B, Anastasiou E, Vagenakis GA, et al. (2003). "Improvement of iodine deficiency after iodine supplementation in schoolchildren of Azerbaijan was accompanied by hypo and hyperthyrotropinemia and increased title of thyroid autoantibodies". Journal of Endocrinological Investigation. 26 (2 Suppl): 43–48. PMID   12762640.
  20. 1 2 Wolff J (January 2001). "Physiology and pharmacology of iodized oil in goiter prophylaxis". Medicine. 80 (1): 20–36. doi: 10.1097/00005792-200101000-00003 . PMID   11204500.
  21. ↑ Medeiros-Neto G, Rubio IG (2016). "Iodine-Deficiency Disorders". Endocrinology: Adult and Pediatric. p. 1597. doi:10.1016/B978-0-323-18907-1.00091-3. ISBN   978-0-323-18907-1.
  22. 1 2 Ingenbleek Y, Jung L, Férard G, Bordet F, Goncalves AM, Dechoux L (November 1997). "Iodised rapeseed oil for eradication of severe endemic goitre". Lancet. 350 (9090): 1542–1545. doi:10.1016/s0140-6736(97)02427-6. PMID   9388412. S2CID   93815.
  23. ↑ Untoro J, Schultink W, Gross R, West CE, Hautvast JG (March 1998). "Efficacy of different types of iodised oil". Lancet. 351 (9104): 752–753. doi:10.1016/S0140-6736(05)78525-1. PMID   9504541. S2CID   45475444.
  24. ↑ Kolbeck KJ (March 2011). "Lipiodol = ethiodol". Journal of Vascular and Interventional Radiology. 22 (3): 419–420. doi:10.1016/j.jvir.2010.10.030. PMID   21277801.
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