Identification
- Summary
Technetium Tc-99m disofenin is a radiopharmaceutical diagnostic agent used for hepatobiliary scans.
- Generic Name
- Technetium Tc-99m disofenin
- DrugBank Accession Number
- DB09164
- Background
Technetium Tc-99m disofenin is a radiopharmaceutical agent used in hepatobiliary imaging for diagnostic purposes. It is well suited for both planar and single photon tomographic scintigraphy to quantitatively measure the function of liver, gallbladder and bile ducts and detect any anatomical changes in the hepatobliary system. It is available as an intravenous injection in a preparation kit under the name Hepatolite. Technetium Tc-99m is a metastable nuclear isomer and disofenin is an iminodiacetic acid derivative with no known pharmacologic actions at the doses recommended. However disofenin is the most commonly used iminodiacetic acid since it has a high liver to renal extraction and its hepatic uptake is not as highly dependent on serum bilirubin levels (a competitive inhibitor for liver uptake) as are other tracers from the iminodiacetic acid.
- Type
- Small Molecule
- Groups
- Approved
- Structure
Structure for Technetium Tc-99m disofenin (DB09164)
- Weight
- Average: 449.321
Monoisotopic: 449.090426499 - Chemical Formula
- C18H26N2O5Tc
- Synonyms
- 99mTc-DISIDA
- 99mTc-Disofenin
- Technetium (99mTc) disofenin
- Technetium Tc 99m Disofenin
- Technetium-99m-Diisopropyliminodiacetic Acid
Pharmacology
- Indication
Technetium Tc99m Disofenin is indicated as a hepatobiliary imaging agent. Hepatolite is indicated in the diagnosis of acute cholecystitis as well as to rule out the occurrence of acute cholecystitis in suspected patients with right upper quadrant pain, fever, jaundice, right upper quadrant tenderness and mass or rebound tenderness, but not limited to these signs and symptoms.
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Diagnostic agent Gallbladder inflammation •••••••••••• •••••••••• ••••••• •••••••••••• ••• •••••••• - Contraindications & Blackbox Warnings
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Technetium Tc99m is a medical radioisotope that is taken up by the liver and accumulates in the hepatobiliary system. Non-visualization of the gallbladder 4 hours after administration of Hepatolite following a 2-6 hour fast and in the presence of activity in the small intestine is indicative of a diagnosis of acute cholecystitis in an otherwise healthy individual. Under the same conditions in an otherwise healthy person, visualization of the gallbladder during a 1 hour scintigraphy is effective in excluding a diagnosis of acute cholecystitis. If the gallbladder is not visualized by 1 hour, scanning must continue for four hours or until the gallbladder is visualized 9. Morphine can be administered to shorten the scanning time and improve visualiation in failure of visualization of the gallbladder with Technetium Tc99m disofenin.
- Mechanism of action
Gallbladder visualization and visualization of intestinal activity occurs by 60 minutes post-injection in individuals with normal hepatobiliary function. Radiopharmaceutical agent is delivered to liver sinusoids via the portal vein and hepatic artery to diffuse through the pores in the endothelial lining to bind to a specific membrane bound carrier, which transports the tracer across the hepatocyte membrane and into the hepatocyte 3. Once inside the hepatocyte, the tracer may be bound by various enzymes and/or undergo metabolism.
- Absorption
In fasting normal individuals, peak liver uptake occurs by 10 minutes post-injection and peak gallbladder accumulation by 30-40 minutes post-injection 9. Hepatic uptake is about 88%.
- Volume of distribution
Technetium Tc99M disofenin is distributed to various tissues including blood, kidney, liver, urinary bladder and predominantly stomach and intestines 8.
- Protein binding
Technetium Tc 99M-iminodiacetic acid complex is thought to bind to plasma proteins, mainly albumin, following intravenous administration which decreases renal excretion and increases hepatic uptake. The radioactive agent and protein complex dissociates after hepatic uptake into the hepatocytes through carrier-mediated non-sodium-dependent membrane transport 7.
- Metabolism
It undergoes radioactive decay.
- Route of elimination
About 9% of the administered activity is excreted in the urine over the first two hours post-injection. The remainder of the activity is essentially quantitatively cleared through the hepatobiliary system 9. Technetium Tc99M disofenin is excreted into the intrahepatic biliary ducts via active transport and is further taken to the extrahepatic bile via choleresis. It may enter the duodenum directly or be stored in the gallbladder for later release. Once inside the intestines, DISIDA does not enter the enterohepatic circulation 3.
- Half-life
Technetium Tc99m decays by isomeric transition with a physical half-life of 6.02 hours 9 but the Technetium Tc99M disofenin complex displays a hepatic elimination half life of 19 minutes 6.
- Clearance
Technetium Tc 99M Disofenin is rapidly cleared from the circulation of normal individuals following intravenous administration; about 8% of the injected activity remains in the circulation 30 minutes post-injection. As the serum bilirubin level increases, the blood clearance becomes progressively delayed 9.
- Adverse Effects
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No long-term animal studies have been performed to evaluate carcinogenic potential or whether Technetium Tc99m Disofenin affects fertility in males or females. There is reported evidence of reproductive toxicity as well as mutagenicity in human leukocytes in vitro. LD50 value in rats following intravenous injection is 7.8mg/kg. Adverse effects from injection include itching at the site of injection progressing to erythema multiforme, and rare cases of nausea and chills.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- Take on an empty stomach. This diagnostic agent should be administered to fasted patients (ideally at least 4 hours post-intake).
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- International/Other Brands
- Hepatolite
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Kit for the Preparation of Technetium Tc99m Disofenin Injection, powder, lyophilized, for solution 20 mg/10mL Intravenous Pharmalucence, Inc. 1982-03-16 2019-09-30 US 
Categories
- ATC Codes
- V09DA01 — Technetium (99mtc) disofenin
- Drug Categories
- Amino Acids
- Amino Acids, Cyclic
- Amino Acids, Peptides, and Proteins
- Compounds used in a research, industrial, or household setting
- Diagnostic Radiopharmaceuticals
- Diagnostic Uses of Chemicals
- Drugs that are Mainly Renally Excreted
- Hepatic and Reticulo Endothelial System
- Imines
- Imino Acids
- Indicators and Reagents
- Laboratory Chemicals
- Organometallic Compounds
- Organotechnetium Compounds
- Radioactive Diagnostic Agent
- Radiopharmaceutical Activity
- Radiopharmaceuticals
- Technetium (99Mtc) Compounds
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as alpha amino acid amides. These are amide derivatives of alpha amino acids.
- Kingdom
- Organic compounds
- Super Class
- Organic acids and derivatives
- Class
- Carboxylic acids and derivatives
- Sub Class
- Amino acids, peptides, and analogues
- Direct Parent
- Alpha amino acid amides
- Alternative Parents
- Alpha amino acids / Phenylpropanes / Cumenes / Anilides / N-arylamides / Dicarboxylic acids and derivatives / Trialkylamines / Secondary carboxylic acid amides / Amino acids / Carboxylic acids show 3 more
- Substituents
- Alpha-amino acid / Alpha-amino acid amide / Amine / Amino acid / Anilide / Aromatic homomonocyclic compound / Benzenoid / Carbonyl group / Carboxamide group / Carboxylic acid show 14 more
- Molecular Framework
- Not Available
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- QTJ2VIW97T
- CAS number
- Not Available
- InChI Key
- JNJYQGLIZTUSCW-NLQOEHMXSA-N
- InChI
- InChI=1S/C18H26N2O5.Tc/c1-11(2)13-6-5-7-14(12(3)4)18(13)19-15(21)8-20(9-16(22)23)10-17(24)25;/h5-7,11-12H,8-10H2,1-4H3,(H,19,21)(H,22,23)(H,24,25);/i;1+2
- IUPAC Name
- 2-[({[2,6-bis(propan-2-yl)phenyl]carbamoyl}methyl)(carboxymethyl)amino]acetic acid (99Tc)technetium
- SMILES
- [99Tc].CC(C)C1=CC=CC(C(C)C)=C1NC(=O)CN(CC(O)=O)CC(O)=O
References
- General References
- Xia CS, Yang XY, Hong GX: 99Tcm-DISIDA hepatobiliary imaging in evaluating gallbladder function in patients with spinal cord injury. Hepatobiliary Pancreat Dis Int. 2007 Apr;6(2):204-7. [Article]
- Spivak W, Sarkar S, Winter D, Glassman M, Donlon E, Tucker KJ: Diagnostic utility of hepatobiliary scintigraphy with 99mTc-DISIDA in neonatal cholestasis. J Pediatr. 1987 Jun;110(6):855-61. [Article]
- Gambhir SS, Hawkins RA, Huang SC, Hall TR, Busuttil RW, Phelps ME: Tracer kinetic modeling approaches for the quantification of hepatic function with technetium-99m DISIDA and scintigraphy. J Nucl Med. 1989 Sep;30(9):1507-18. [Article]
- Fong YC, Hsu HC, Sun SS, Kao A, Lin CC, Lee CC: Impaired gallbladder function in spinal cord injury on quantitative Tc-99m DISIDA cholescintigraphy. Abdom Imaging. 2003 Jan-Feb;28(1):87-91. [Article]
- Ascher SA, Sarkar SD, Spivak WB: Hepatic uptake of technetium-99m diisopropyl iminodiacetic acid (DISIDA) is not impaired by very high serum bilirubin levels. Clin Nucl Med. 1988 Jan;13(1):1-3. [Article]
- Krishnamurthy GT, Turner FE: Pharmacokinetics and clinical application of technetium 99m-labeled hepatobiliary agents. Semin Nucl Med. 1990 Apr;20(2):130-49. [Article]
- Krishnamurthy S, Krishnamurthy GT: Technetium-99m-iminodiacetic acid organic anions: review of biokinetics and clinical application in hepatology. Hepatology. 1989 Jan;9(1):139-53. [Article]
- Chervu LR, Nunn AD, Loberg MD: Radiopharmaceuticals for hepatobiliary imaging. Semin Nucl Med. 1982 Jan;12(1):5-17. [Article]
- Dailymed Hepatolite product information (FDA Label) [Link]
- External Links
- FDA label
- Download (1010 KB)
- MSDS
- Download (49.8 KB)
Clinical Trials
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, powder, lyophilized, for solution Intravenous 20 mg/10mL - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.0463 mg/mL ALOGPS logP 0.13 ALOGPS logP 1.01 Chemaxon logS -3.9 ALOGPS pKa (Strongest Acidic) 3.11 Chemaxon pKa (Strongest Basic) 2.41 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 6 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 106.94 Å2 Chemaxon Rotatable Bond Count 9 Chemaxon Refractivity 94.9 m3·mol-1 Chemaxon Polarizability 37.21 Å3 Chemaxon Number of Rings 1 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Not Available
- Chromatographic Properties
Collision Cross Sections (CCS)
Not Available
Drug created at October 05, 2015 17:02 / Updated at October 09, 2021 02:48