Technetium Tc-99m disofenin

Identification

Name
Technetium Tc-99m disofenin
Accession Number
DB09164
Type
Small Molecule
Groups
Approved
Description

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.

Structure
Thumb
Synonyms
  • 99mTc-DISIDA
  • 99mTc-Disofenin
  • Technetium (99mTc) disofenin
  • Technetium Tc 99m Disofenin
  • Technetium-99m-Diisopropyliminodiacetic Acid
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Kit for the Preparation of Technetium Tc99m DisofeninInjection, powder, lyophilized, for solution20 mg/10mLIntravenousPharmalucence, Inc.1982-03-16Not applicableUs
International/Other Brands
Hepatolite
Categories
UNII
QTJ2VIW97T
CAS number
Not Available
Weight
Average: 449.321
Monoisotopic: 449.090426499
Chemical Formula
C18H26N2O5Tc
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

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.

Pharmacodynamics

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].

Toxicity

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.

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AbacavirAbacavir may decrease the excretion rate of Technetium Tc-99m disofenin which could result in a higher serum level.
AcarboseAcarbose may decrease the excretion rate of Technetium Tc-99m disofenin which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Technetium Tc-99m disofenin which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Technetium Tc-99m disofenin which could result in a higher serum level.
AcetaminophenAcetaminophen may decrease the excretion rate of Technetium Tc-99m disofenin which could result in a higher serum level.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Technetium Tc-99m disofenin which could result in a higher serum level.
AclidiniumAclidinium may decrease the excretion rate of Technetium Tc-99m disofenin which could result in a higher serum level.
AcrivastineTechnetium Tc-99m disofenin may decrease the excretion rate of Acrivastine which could result in a higher serum level.
AcyclovirAcyclovir may decrease the excretion rate of Technetium Tc-99m disofenin which could result in a higher serum level.
AdefovirAdefovir may decrease the excretion rate of Technetium Tc-99m disofenin which could result in a higher serum level.
Food Interactions
Not Available

References

General References
  1. 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. [PubMed:17374583]
  2. 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. [PubMed:3585600]
  3. 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. [PubMed:2769404]
  4. 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. [PubMed:12483393]
  5. 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. [PubMed:3349693]
  6. Krishnamurthy GT, Turner FE: Pharmacokinetics and clinical application of technetium 99m-labeled hepatobiliary agents. Semin Nucl Med. 1990 Apr;20(2):130-49. [PubMed:2184521]
  7. 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. [PubMed:2642291]
  8. Chervu LR, Nunn AD, Loberg MD: Radiopharmaceuticals for hepatobiliary imaging. Semin Nucl Med. 1982 Jan;12(1):5-17. [PubMed:6281914]
  9. Dailymed Hepatolite product information (FDA Label) [Link]
External Links
PubChem Compound
11430828
PubChem Substance
347827828
ATC Codes
V09DA01 — Technetium (99mtc) disofenin
FDA label
Download (1010 KB)
MSDS
Download (49.8 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, powder, lyophilized, for solutionIntravenous20 mg/10mL
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0463 mg/mLALOGPS
logP0.13ALOGPS
logP1.01ChemAxon
logS-3.9ALOGPS
pKa (Strongest Acidic)3.11ChemAxon
pKa (Strongest Basic)2.41ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area106.94 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity94.9 m3·mol-1ChemAxon
Polarizability37.21 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

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 amide / Alpha-amino acid / Cumene / Phenylpropane / Anilide / N-arylamide / Monocyclic benzene moiety / Dicarboxylic acid or derivatives / Benzenoid / Tertiary amine
show 14 more
Molecular Framework
Not Available
External Descriptors
Not Available

Drug created on October 05, 2015 11:02 / Updated on November 02, 2018 06:59