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SeHCAT (23-seleno-25-homotaurocholic acid, selenium homocholic acid taurine, or tauroselcholic acid) is a drug used in a clinical test to diagnose bile acid malabsorption.


Development

SeHCAT is a taurine-conjugated
bile acid Bile acids are steroid acids found predominantly in the bile of mammals and other vertebrates. Diverse bile acids are synthesized in the liver in peroxisomes. Bile acids are conjugated with taurine or glycine residues to give anions called bile ...
analog which was synthesized for use as a
radiopharmaceutical Radiopharmaceuticals, or medicinal radiocompounds, are a group of pharmaceutical drugs containing radioactive isotopes. Radiopharmaceuticals can be used as diagnostic and therapeutic agents. Radiopharmaceuticals emit radiation themselves, which ...
to investigate ''in vivo'' the
enterohepatic circulation Enterohepatic circulation is the circulation of biliary acids, bilirubin, drugs or other substances from the liver to the bile, followed by entry into the small intestine, absorption by the enterocyte and transport back to the liver. Enterohepa ...
of
bile salts Bile acids are steroid acids found predominantly in the bile of mammals and other vertebrates. Diverse bile acids are synthesized in the liver in peroxisomes. Bile acids are conjugated with taurine or glycine residues to give anions called bile ...
. By incorporating the gamma-emitter 75Se into the SeHCAT molecule, the retention in the body or the loss of this compound into the feces could be studied easily using a standard gamma camera, available in most clinical
nuclear medicine Nuclear medicine (nuclear radiology, nucleology), is a medical specialty involving the application of radioactivity, radioactive substances in the diagnosis and treatment of disease. Nuclear imaging is, in a sense, ''radiology done inside out'', ...
departments. SeHCAT has been shown to be absorbed from the gut and excreted into the bile at the same rate as
cholic acid Cholic acid, also known as 3α,7α,12α-trihydroxy-5β-cholan-24-oic acid is a primary bile acid that is insoluble in water (soluble in alcohol and acetic acid), it is a white crystalline substance. Salts of cholic acid are called cholates. Cho ...
, one of the major natural bile acids in humans. It undergoes secretion into the biliary tree, gallbladder and intestine in response to food, and is reabsorbed efficiently in the ileum, with kinetics similar to natural bile acids. It was soon shown to be the most convenient and accurate method available to assess and measure
bile acid Bile acids are steroid acids found predominantly in the bile of mammals and other vertebrates. Diverse bile acids are synthesized in the liver in peroxisomes. Bile acids are conjugated with taurine or glycine residues to give anions called bile ...
turnover in the intestine. SeHCAT testing was commercially developed by Amersham International Ltd ( Amersham plc is now part of GE Healthcare Medical Diagnostics division) for clinical use to investigate
malabsorption Malabsorption is a state arising from abnormality in absorption of food nutrients across the gastrointestinal (GI) tract. Impairment can be of single or multiple nutrients depending on the abnormality. This may lead to malnutrition and a varie ...
in patients with
diarrhea Diarrhea (American English), also spelled diarrhoea or diarrhœa (British English), is the condition of having at least three loose, liquid, or watery bowel movements in a day. It often lasts for a few days and can result in dehydration d ...
. This test has replaced 14C-labeled glycocholic acid (or taurocholic acid) breath tests and fecal bile acid measurements, which now have no place in the routine clinical investigation of
malabsorption Malabsorption is a state arising from abnormality in absorption of food nutrients across the gastrointestinal (GI) tract. Impairment can be of single or multiple nutrients depending on the abnormality. This may lead to malnutrition and a varie ...
.


Procedure

A capsule containing radiolabelled 75SeHCAT (with 370 kBq of Selenium-75 and less than 0.1 mg SeHCAT) is taken orally with water, to ensure passage of the capsule into the gastrointestinal tract. The physical half life of 75Se is approximately 118 days; activity is adjusted to a standard reference date. Patients may be given instructions to fast prior to capsule administration; there is significant variation in clinical practice in this regard. The effective dose of radiation for an adult given 370 kBq of SeHCAT is 0.26 mSv. (For comparison, the radiation exposure from an abdominal
CT scan A computed tomography scan (CT scan), formerly called computed axial tomography scan (CAT scan), is a medical imaging technique used to obtain detailed internal images of the body. The personnel that perform CT scans are called radiographers or ...
is quoted at 5.3 mSv and annual background exposure in the UK 1-3 mSv.) Measurements were originally performed with a whole-body counter but are usually performed now with an uncollimated gamma camera. The patient is scanned supine or prone with anterior and posterior acquisition from head to thigh 1 to 3 hours after taking the capsule. Scanning is repeated after 7 days. Background values are subtracted and care must be taken to avoid external sources of radiation in a nuclear medicine department. From these measurements, the percent retention of SeHCAT at 7 days is calculated. A 7-day SeHCAT retention value greater than 15% is considered to be normal, with values less than 15% signifying excessive bile acid loss, as found in bile acid malabsorption. With more frequent measurements, it is possible to calculate SeHCAT retention whole-body half-life; this is not routinely measured in a clinical setting. A half-life of greater than 2.8 days has been quoted as normal.


Clinical use

The SeHCAT test is used to investigate patients with suspected bile acid malabsorption, who usually experience chronic diarrhea, often passing watery feces 5 to 10 times each day. When ileum has been removed following surgery, or is inflamed in
Crohn's disease Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract. Symptoms often include abdominal pain, diarrhea, fever, abdominal distension, and weight loss. Complications outside of the ...
, the 7-day SeHCAT retention usually is abnormal, and most of these patients will benefit from treatment with bile acid sequestrants. The
enterohepatic circulation Enterohepatic circulation is the circulation of biliary acids, bilirubin, drugs or other substances from the liver to the bile, followed by entry into the small intestine, absorption by the enterocyte and transport back to the liver. Enterohepa ...
of bile acids is reduced in these patients with ileal abnormalities and, as the normal bile acid retention exceeds 95%, only a small degree of change is needed. Bile acid malabsorption can also be secondary to
cholecystectomy Cholecystectomy is the surgical removal of the gallbladder. Cholecystectomy is a common treatment of symptomatic gallstones and other gallbladder conditions. In 2011, cholecystectomy was the eighth most common operating room procedure performed i ...
, vagotomy and other disorders affecting intestinal motility or digestion such as radiation enteritis,
celiac disease Coeliac disease (British English) or celiac disease (American English) is a long-term autoimmune disorder, primarily affecting the small intestine. Patients develop intolerance to gluten, which is present in foods such as wheat, rye, spel ...
, and
small intestinal bacterial overgrowth Small intestinal bacterial overgrowth (SIBO), also termed bacterial overgrowth, or small bowel bacterial overgrowth syndrome (SBBOS), is a disorder of excessive bacterial growth in the small intestine. Unlike the colon (or large bowel), which is r ...
. A similar picture of chronic diarrhea, an abnormal SeHCAT retention and a response to bile acid sequestrants, in the absence of other disorders of the intestine, is characteristic of idiopathic bile acid malabsorption – also called primary bile acid diarrhea. These patients are frequently misdiagnosed as having the
irritable bowel syndrome Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by a group of symptoms that commonly include abdominal pain, abdominal bloating, and changes in the consistency of bowel movements. These symptoms may ...
, as clinicians fail to recognize the condition, do not think of performing a SeHCAT test, or do not have it available. There have been at least 18 studies of the use of SeHCAT testing in diarrhea-predominant
irritable bowel syndrome Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by a group of symptoms that commonly include abdominal pain, abdominal bloating, and changes in the consistency of bowel movements. These symptoms may ...
patients. When these data were combined, 32% of 1223 patients had a SeHCAT 7-day retention of less than 10%, and 80% of these reported a response to cholestyramine, a
bile acid sequestrant The bile acid sequestrants are a group of resins used to bind certain components of bile in the gastrointestinal tract. They disrupt the enterohepatic circulation of bile acids by combining with bile constituents and preventing their reabsorption f ...
.


References


External links


GE Healthcare SeHCAT site
{{Diagnostic radiopharmaceuticals Diagnostic gastroenterology Radiopharmaceuticals Gastroenterology Bile acids Cholanes Organoselenium compounds Selenium(−II) compounds Selenoethers