99mTc-Mebrofenin (Br-IDA)

^99mTc-mebrofenin is a radiopharmaceutical agent used in nuclear medicine imaging to perform scans of the liver, gallbladder, and bile duct, which are essential components of the hepatobiliary system responsible for bile excretion. This agent is specifically designed for diagnosing hepatobiliary dysfunction and differentiating jaundice.

The quantitative measurement of liver function remains a holy grail of modern medicine. From a molecular perspective, liver function can be estimated by the activity of membrane transporters expressed in hepatocytes. An array of membrane transporters of the solute carrier (SLC) and adenosine triphosphate–binding cassette (ABC) superfamilies control the hepatobiliary clearance of many endogenous and exogenous compounds. Several SLC influx transporters, including the organic anion–transporting polypeptide (OATP) transporters OATP1B1 and OATP1B3, are expressed in the sinusoidal (blood-facing) membrane of hepatocytes, where they mediate the uptake of their substrates from blood into the liver. ABC efflux transporters expressed at the canalicular (bile-facing) membrane of hepatocytes, such as the multidrug resistance–associated protein 2 (MRP2) or the bile salt export pump, control the biliary excretion of solutes and bile acids. Other ABC transporters are expressed in the sinusoidal hepatocyte membrane, where they mediate the backflux of solutes from hepatocytes into blood.

^99mTc-mebrofenin benefits from improved pharmacokinetic properties such fast blood clearance caused by rapid and predominant uptake by the liver followed by biliary excretion, with minimal urinary excretion. Radiolabeling of ^99mTc-mebrofenin from commercial kits is straightforward, yielding high radiochemical purity and stability. ^99mTc-mebrofenin scintigraphy is therefore widely used in nuclear medicine to explore the dynamics of biliary excretion or estimate hepatic extraction capacity to assess biliary disorders, such as bile duct obstruction, cholecystitis, or gallbladder dysfunction.

The use of ^99mTc-mebrofenin is crucial in the diagnosis of various conditions affecting the hepatobiliary system, including hepatitis, hepatic duct occlusion, gallbladder functional disorders, inflammation of the hepatobiliary system, and cholecystitis. By administering ^99mTc-mebrofenin and performing imaging scans, healthcare professionals can visualize the function and structure of these organs and identify any abnormalities or dysfunctions present.

Overall, ^99mTc-mebrofenin plays a vital role in the non-invasive assessment of hepatobiliary diseases and is an important tool in the diagnostic workup of patients presenting with symptoms related to liver, gallbladder, or bile duct disorders.

Description

^99mTc-Mebrofenin (^99mTc-3-bromo-2,4,6-trimethyl-IDA, ^99mTc-3-bromo-2,4,6- trimethylimino-diacetic acid, ^99mTc-BTM-IDA, ^99mTc-Br-IDA, ^99mTc-SQ26,962, ^99mTc-TBIDA, ^99mTc-MBrIDA, ^99mTc-N-[3-bromo-2,4,6 trimethyl acetanilido-iminodiacetate; trimethyl- bromo-IDA, ^99mTc-MBrIDA) is a generic SPECT agent useful for the visualization of hepatobiliary system and evaluation of the liver function from the ^99mTc-IDA tracer family.

Clinical applications

Mebrofenin is used to perform scans of the liver, the gallbladder and the bile duct which are usual paths of bile excretion. This agent is indicated for diagnosis of hepatobiliary dysfunction and for differentiation of jaundice. It is used in diagnosis of hepatitis, hepatic duct occlusion, gallbladder functional disorders, inflammation of the hepatobiliary system, and cholecystitis.

Availability and price

Mebrofenin is available under the names BRIDA (Pars Isotope), Bridatec (GE Healthcare, EU authorization obtained in 1995), Bromezida (DiaMed, Russian MA obtained in 1991), Bromo-Biliaron (Medi-Radiopharma), Cholecis (IBA Molecular, rights transferred to Mediam), Cholediam^® (Mediam; EU MA 2000), Choletec^® (Bracco; marketed since 1987), Mebrofenin-kit (Pharmalucence), PoltechMBrIDA (POLATOM), TCK-39 (BRIT).

Bracco also offers Kinevac (Sincalide) a cholecystopancreatic-gastrointestinal peptide hormone for parenteral administration that has a physiological effect on the gallbladder. It stimulates gallbladder contraction during diagnostic imaging examinations with ^99mTc-Mebrofenin and results are more reproducible than fatty acid meal.

In Europe, lowest dose price starts at EUR 50, but prices are increasing. In 2020 in the USA, a dose of Mebrofenin is charged around US$ 60.

Competition

There are several marketed products alongside to ^99mTc-Mebrofenin available for the imaging of the hepatobiliary tract including ^99mTc-Disofenin, ^99mTc-EHIDA. All of them are generics.

Comments

Several IDA analogues have been developed alongside the marketed ones, including ^99mTc-HEPIDA, ^99mTc-Etifenin, ^99mTc-PIPIDA or ^99mTc-Galtifenin. It seems that ^99mTc-Mebrofenin remains the tracer with the best performance and which is replacing almost all other tracers.

1. DOI: https://doi.org/10.2967/jnumed.120.261321 ↩︎