Medication Guide App

Technetium Tc 99m Disofenin (Systemic)


VA CLASSIFICATION
Primary: DX201

Commonly used brand name(s): Hepatolite.

Another commonly used name is
technetium Tc 99m DISIDA .
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

Not commercially available in Canada.



Category:


Diagnostic aid, radioactive (hepatobiliary disorders)—

Indications

Accepted

Hepatobiliary imaging, radionuclide—Technetium Tc 99m disofenin is indicated as a hepatobiliary imaging agent for the evaluation of hepatobiliary tract patency to differentiate jaundice resulting from hepatocellular causes from jaundice resulting from partial or complete biliary obstruction; to differentiate extrahepatic biliary atresia from neonatal hepatitis; to detect cystic duct obstruction associated with acute cholecystitis; and to detect bile leaks. {01} {18} {19} {23} {26} {32} {33} {34} {35} {37}
—Also, technetium Tc 99m disofenin may be useful to detect intrahepatic cholestasis and to distinguish it from other hepatobiliary diseases that involve hepatocyte damage. {20} {39}


Physical Properties

Nuclear data:



Radionuclide
(half-life)
Decay
constant
Mode
of
decay
Principal
photon
emissions
(keV)
Mean
number of
emissions/
disintegration
(³0.01)
Tc 99m
(6.0 hr)
0.1151 h -1
Isomeric
transition to
Tc 99
Gamma
(18)
0.062
Gamma
(140.5)
0.891


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    Disofenin: 350.41 {03}

Mechanism of action/Effect:

Based on the clearance of most of the administered activity through the hepatobiliary system. Following intravenous administration, technetium Tc 99m–labeled IDA derivatives, such as disofenin, become bound to plasma proteins (mainly albumin). In the liver, in the space of Disse, technetium Tc 99m disofenin becomes dissociated from the proteins and enters the hepatocyte by a mechanism similar to that of serum bilirubin. Technetium Tc 99m disofenin traverses the hepatocyte unmetabolized and enters the bile canaliculi. Flow beyond the canaliculi is influenced to a large extent by the tone of the sphincter of Oddi and the patency of the bile ducts. Clear visualization of the gallbladder and intestines with technetium Tc 99m disofenin demonstrates hepatobiliary tract patency. {01} {37} {39}

Distribution:

In circulatory system, with rapid clearance; however, a percentage of the radiopharmaceutical (about 8%) remains in circulation 30 minutes after injection. It is cleared from blood by normal hepatic cells within 10 to 20 minutes. Excreted into bile and stored in gallbladder. The radiopharmaceutical is excreted through the hepatobiliary tract into the intestine. A fraction of the radiopharmaceutical is excreted into the urine. The fraction excreted into the urine is dependent on the extent of biliary disease. {01} {02} {11} {16} {39}

Time to radioactivity visualization


In patients with normal hepatobiliary function (fasting state) {01} {16} {39}:

Gallbladder: 10 to 20 minutes.

Intestines: 30 to 60 minutes.


Note: Delayed visualization or nonvisualization may occur during the period immediately following a meal or after prolonged fasting. {01}


Radiation dosimetry:
{15}

Organ
Estimated absorbed radiation dose*
With normal
hepatobiliary function

With parenchymal
liver disease

mGy/
MBq
rad/
mCi
mGy/
MBq
rad/
mCi
Gallbladder wall
0.11
0.41
0.035
0.13
Large intestine
wall (upper)
0.092
0.34
0.033
0.12
Large intestine
wall (lower)
0.062
0.23
0.024
0.089
Small intestine
0.052
0.19
0.019
0.070
Bladder wall
0.023
0.085
0.069
0.26
Ovaries
0.020
0.074
0.0099
0.037
Liver
0.015
0.056
0.010
0.037
Uterus
0.013
0.048
0.011
0.041
Red marrow
0.0070
0.026
0.0038
0.014
Kidneys
0.0063
0.023
0.0066
0.024
Stomach wall
0.0061
0.023
0.0027
0.010
Pancreas
0.0057
0.021
0.0028
0.010
Adrenals
0.0032
0.012
0.0021
0.0078
Bone surfaces
0.0026
0.0096
0.0017
0.0063
Spleen
0.0026
0.0096
0.0015
0.0056
Testes
0.0015
0.0056
0.0025
0.0093
Breast
0.00061
0.0023
0.00056
0.0021
Thyroid
0.00012
0.00044
0.00023
0.00085
Other tissue
0.0030
0.011
0.0021
0.0078


Radionuclide
Effective dose*
With normal
hepatobiliary function

With parenchymal
liver disease

mSv/
MBq
rem/
mCi
mSv/
MBq
rem/
mCi
Tc 99m
0.024
0.089
0.013
0.048
* For adults; intravenous injection of technetium Tc 99m–labeled iminodiacetic acid (IDA) derivatives. Data based on the International Commission on Radiological Protection (ICRP) Publication 53—Radiation dose to patients from radiopharmaceuticals. {15}

Elimination:
    Primarily fecal; about 9% eliminated in the urine within 2 hours. {01} {02}

Note: In patients with hepatocellular disease or biliary obstruction, elimination through the urinary tract may be greatly increased. {02}



Precautions to Consider

Cross-sensitivity and/or related problems

Patients sensitive to amide-type local anesthetics may be sensitive to technetium Tc 99m disofenin also. {11}

Carcinogenicity/Mutagenicity

Long-term animal studies to evaluate carcinogenic or mutagenic potential of technetium Tc 99m disofenin have not been performed. {01}

Pregnancy/Reproduction

Pregnancy—
Tc 99m (as free pertechnetate) crosses the placenta. Studies have not been done with technetium Tc 99m disofenin in humans.

The possibility of pregnancy should be assessed in women of child-bearing potential. Clinical situations exist where the benefit to the patient and fetus, based on information derived from radiopharmaceutical use, outweighs the risks from fetal exposure to radiation. In these situations, the physician should use discretion and reduce the radiopharmaceutical administered activity to the lowest possible amount. {17}

Studies have not been done in animals.

FDA Pregnancy Category C. {01}

Breast-feeding

Although it is not known whether technetium Tc 99m disofenin is distributed into breast milk, it is known that Tc 99m as free pertechnetate is distributed into breast milk. Based on the assumption that the Tc 99m in breast milk is in the form of pertechnetate and based on the effective half-life of the radionuclide in breast milk, the daily volume of milk, a dose factor relating the radionuclide to its critical organ (thyroid) in the nursing infant, and the maximum permissible dose to that organ, a guideline has been proposed. According to this guideline, it has been calculated that nursing can be safely resumed when the concentration in breast milk reaches 30.3 × 10 -4 megabecquerels (8.2 × 10 -2 microcuries) per mL. {12}This level of activity is probably reached, in the majority of patients, within 12 to 24 hours after administration of technetium Tc 99m–labeled radiopharmaceuticals. {16} {22} {39}

Pediatrics

Diagnostic studies performed to date using technetium Tc 99m disofenin have not demonstrated pediatrics-specific problems that would limit its usefulness in children. However, there have been no specific studies evaluating the safety and efficacy of technetium Tc 99m disofenin in pediatric patients. When this radiopharmaceutical is used in children, the diagnostic benefit should be judged to outweigh the potential risk of radiation. {17} {39} {40} {41} {42} {43}


Geriatrics


Appropriate studies on the relationship of age to the effects of technetium Tc 99m disofenin have not been performed in the geriatric population. However, no geriatrics-specific problems have been documented to date.

Drug interactions and/or related problems
See Diagnostic interference.

Diagnostic interference
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With results of this test

Due to other medications
Alcohol or
Anticholinergics or other medications with anticholinergic action (See Appendix II ) or
Bethanechol or
Somatostatin    (may decrease gallbladder emptying thus delaying gallbladder clearance of technetium Tc 99m disofenin)


Erythromycin    (nonvisualization of gallbladder may occur due to erthromycin-induced hepatotoxicity)

{44}{45}
Nicotinic acid    (chronic, high-dose nicotinic acid therapy may result in poor extraction and elimination of the radiopharmaceutical, mimicking intrinsic hepatocellular disease)

{10}{13}{14}{44}
Opioid (narcotic) analgesics, especially butorphanol, morphine, and meperidine    (delivery of technetium Tc 99m disofenin to the small bowel may be prevented by the opioid analgesics because of constriction of the sphincter of Oddi and increased biliary tract pressure caused by these medications; these actions result in delayed intestinal visualization, which resembles that caused by obstruction of the common bile duct; however, the use of intravenous morphine has been shown to help in the diagnosis of acute cholecystitis when conditions that delay or prevent gallbladder visualization are present {01} {07} {14} {16} {18} {26} {27} {31} {39} {44})


Parenteral alimentation    (may give false-positive diagnosis of cystic duct obstruction due to stasis of bile in the gallbladder {11} {14} {16} {28} {44})


Due to medical problems or conditions
Fasting, prolonged or
Pancreatitis, acute    (may give false-positive results [nonvisualization or delayed visualization of gallbladder] of cystic duct obstruction due to stasis of bile in gallbladder {11} {16} {26} {39})


Hepatocellular disease    (nonvisualization or delayed visualization of gallbladder may occur {16})


Post-prandial state, especially with ingestion of fatty meals    (ingestion of a fatty meal immediately before test may give false-positive results [nonvisualization of gallbladder] of cystic duct obstruction due to gallbladder contraction stimulated by meal ingestion {16} {39})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).

See also Diagnostic interference.

Risk-benefit should be considered when the following medical problem exists
Sensitivity to amide-type local anesthetics or to the radiopharmaceutical preparation


Side/Adverse Effects
There are no known side/adverse effects associated with the use of technetium Tc 99m disofenin. {01} {16}



Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Radiopharmaceuticals (Diagnostic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Description of use
Action in the body: Clearance of radioactive disofenin from blood through hepatobiliary tract

Visualization of radioactivity in intestinal tract and gallbladder shows absence of obstruction of bile ducts

Small amounts of radioactivity used in diagnosis; radiation received is low and considered safe

Before having this test
»   Conditions affecting use, especially:
Sensitivity to amide-type local anesthetics or to the radiopharmaceutical preparation

Pregnancy—Technetium Tc 99m (as free pertechnetate) crosses placenta; risk to fetus from radiation exposure as opposed to benefit derived from use should be considered





Breast-feeding—Not known if technetium Tc 99m disofenin distributed into breast milk, but Tc 99m as free pertechnetate is distributed into breast milk; temporary discontinuation of nursing may be recommended because of risk to infant from radiation exposure





Use in children—Risk from radiation exposure as opposed to benefit derived from use should be considered


Preparation for this test
Fasting for at least 2, and preferably 4 hours before test to prevent gallbladder nonvisualization

Precautions after having this test
No special precautions


General Dosing Information
Radiopharmaceuticals are to be administered only by or under the supervision of physicians who have had extensive training in the safe use and handling of radioactive materials and who are authorized by the Nuclear Regulatory Commission (NRC) or the appropriate Agreement State agency, if required, or, outside the U.S., the appropriate authority. {23}

Administration of phenobarbital (5 mg per kg of body weight [mg/kg] in 2 fractions) for at least 5 days prior to hepatobiliary imaging may enhance and accelerate biliary uptake and excretion of the radiopharmaceutical in the differential diagnosis of extrahepatic atresia from neonatal hepatitis. This will enable determination of the status of the extrahepatic biliary tract in the jaundiced neonate within 24 hours. {24} {25} {36}

Fasting is recommended for at least 2, and preferably 4 hours before the examination since nonvisualization of the gallbladder may result if gallbladder contraction has been stimulated by the ingestion of food. {01} {14} {39} {41} {42}

Prolonged fasting (e.g., more than 24 hours) may result in a false-positive hepatobiliary scan (i.e., nonvisualization of the gallbladder despite a patent cystic duct) due to the development of increased intraluminal gallbladder pressure (biliary stasis or sludge), which reduces radiotracer flow to the gallbladder. To avoid this, prior administration of a cholecystokinetic agent, such as sincalide or cholecystokinin (CCK-8), to induce contraction of the gallbladder is recommended for pre-emptying the gallbladder before the injection of technetium Tc 99m disofenin. Whenever there is doubt about the dietary history of the patient, especially in emergency situations, a cholecystokinetic agent should be administered. {36} {39}

In patients receiving parenteral alimentation, the relative inactivity of the gallbladder results in bile stasis and the formation of thick viscous bile (sludge), which reduces the flow of the radiotracer into the gallbladder. Pretreatment with a cholecystokinetic agent (e.g., intravenous sincalide 0.02 to 0.04 mcg per kg of body weight [mcg/kg]) may be useful to empty stored bile from the gallbladder, and thus may prevent a false-positive hepatobiliary scan. {36} {37} {39}

In patients demonstrating technetium Tc 99m disofenin localization in the gallbladder, a cholecystokinetic agent (e.g., intravenous sincalide 0.02 to 0.04 mcg/kg of body weight) may be useful to stimulate gallbladder contraction and thereby evaluate the contractile function of the gallbladder. Quantitation of gallbladder emptying yields the ejection fraction (³ 35% is usually considered normal). {39} {46}

Imaging is performed immediately following technetium Tc 99m disofenin administration, and is usually completed in 60 to 90 minutes. Imaging for up to 4 hours or longer may be necessary if no gallbladder or intestinal activity is seen at the earlier times. {01} {16}

When there is no visualization of the gallbladder within an hour of administration of technetium Tc 99m disofenin, but the radiotracer is seen within the small bowel in patients suspected of having acute cholecystitis, morphine sulfate (0.04 mg/kg diluted in 10 mL saline) may be injected intravenously to help confirm the diagnosis. The diagnosis of acute cholecystitis is confirmed if nonvisualization of the gallbladder persists after morphine is administered. Although morphine-augmented cholescintigraphy may cause false-positive and false-negative results in some patients (e.g., acalculous cholecystitis), it may be useful in critically ill patients or patients who have been on prolonged fasting or who are receiving parenteral alimentation. {18} {26} {27} {28} {29} {36} {39} {47} {48} {49}

Safety considerations for handling this radiopharmaceutical
Improper handling of this radiopharmaceutical may cause radioactive contamination. Guidelines for handling radioactive material have been prepared by scientific, professional, state, federal, and international bodies and are available to the specially qualified and authorized users who have access to radiopharmaceuticals. {50}


Parenteral Dosage Forms

TECHNETIUM Tc 99m DISOFENIN INJECTION USP

Usual adult and adolescent administered activity
Hepatobiliary imaging
Nonjaundiced patients: Intravenous, 37 to 185 megabecquerels (1 to 5 millicuries) by slow injection. {01}

Patients with serum bilirubin concentration > 0.08 mmol per L (5 mg per dL): Intravenous, 111 to 296 megabecquerels (3 to 8 millicuries) by slow injection. {01}


Usual pediatric administered activity
Hepatobiliary imaging
Dosage must be individualized by physician. The minimum recommended administered activity is 37 megabecquerels (1 millicurie), intravenously. {38} {39}


Usual geriatric administered activity
See Usual adult and adolescent administered activity.

Strength(s) usually available
U.S.—


20 mg disofenin, 0.24 mg (minimum) stannous chloride, and 0.6 mg total tin (maximum tin as stannous chloride) in lyophilized form under nitrogen atmosphere, per reaction vial (Rx) [Hepatolite{01}]

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Protect from freezing.

Preparation of dosage form:
To prepare injection, an oxidant-free sodium pertechnetate Tc 99m solution is used. See manufacturer's package insert for instructions.

Stability:
Injection should be administered within 6 hours after preparation.

Note: Caution—Radioactive material.




Revised: 08/02/1994



References

Note: All references used in the development and earlier revisions of this monograph have not yet been incorporated into the computer database and, therefore, are not listed below. Citations for information not yet referenced in the monograph will be provided upon request.

  1. Hepatolite package insert (New England Nuclear—US), Rev 1/83.
  1. Chilton HM, Witcofski RL. Nuclear pharmacy—An introduction to the clinical application of radiopharmaceuticals. Philadelphia: Lea & Febiger, 1986: 99-101.
  1. Drug Nomenclature Committee of the USP Committee of Revision. USAN and the USP dictionary of drug names.
  1. MIRD Pamphlet No. 10.
  1. Brown PH, Krishnamurthy GT, Bobba VR, et al. Radiation-dose calculation for five Tc-99m IDA hepatobiliary agents. J Nucl Med 1982; 23(11): 1025-30.
  1. Reviewers' comments for Technetium Tc 99m Disofenin.
  1. Hladik WB, et al., Drug-induced changes in biodistribution. Semin Nucl Med, April 1982; 201.
  1. Lamb RB, Nelson JA, Englert E, et al. Concentration of Tc 99m-HIDA and iopanoic glucuronide by the gallbladder. Invest Radiol 1984; 19(5): 455-7.
  1. Pharmacy Int'l 1985 Dec: 297.
  1. Panel comments 5/25/87; 1/15/86.
  1. Reviewers' comments on Tc 99m Lidofenin monograph, USP DI.
  1. USP Radiopharmaceuticals Advisory Panel (as per 1/88 meeting).
  1. J Nucl Med 1981; 22: 746-7.
  1. Hladik WB, Saha GB, Study KT. Essentials of nuclear medicine science. Baltimore: Williams & Wilkins, 1987: 126-7, 191-3, 417.
  1. Task Group of Committee 2 of the International Commission on Radiological Protection. Annals of the ICRP. ICRP Publication 53—Radiation dose to patients from radiopharmaceuticals. New York: Pergamon Press, 1988: 201-5.
  1. Swanson DP, Chilton HM, Thrall JH, editors. Pharmaceuticals in medical imaging. New York: Macmillan Publishing Company, 1990: 471-83.
  1. USP Radiopharmaceuticals Panel meeting on 05/08/91.
  1. Fink-Bennett D, Balon H, Robbins T, et al. Morphine-augmented cholescintigraphy: its efficacy in detecting acute cholecystitis. J Nucl Med 1991; 32: 1231-3.
  1. Silfen D. The role of hepatobiliary imaging in the evaluation and management of patients with common bile duct gallstones. J Nucl Med 1991; 32: 1261-5.
  1. Kuni CC, Engeler CM, Nakhleh RE, et al. Correlation of technetium-99m-DISIDA hepatobiliary studies with biopsies in liver and transplant patients. J Nucl Med 1991; 32: 1545-7.
  1. Sarkar SD. Hepatic clearance of technetium-99m-iminodiacetic acid derivatives in hyperbilirubinemic states [editorial]. J Nucl Med 1991; 32: 1551.
  1. Romney BM, et al. Radionuclide administration to nursing mothers. Mathematically derived guidelines. Radiology 1986; 160: 549-54.
  1. USP Radiopharmaceuticals Panel meeting on 08/04/92.
  1. Sharp HL, Mirkin BL. Effect of phenobarbital on hyperbilirubinemia, bile acid metabolism, and microsomal enzyme activity in chronic intrahepatic cholestasis of childhood. J Pediatr 1972; 81: 116-26.
  1. Yaffe SJ, Levy G, Matsuzawa T, et al. Enhancement of glucuronide conjugating capacity in a hyperbilirubinemic infant due to apparent enzyme induction by phenobarbital. N Engl J Med 1966; 275: 1461-6.
  1. Kim EE, Podoloff D. Is morphine injection useful in the scintigraphic diagnosis of acute cholecystitis (editorial)? J Nucl Med 1991; 32(6): 1233-4.
  1. Flancbaum L, Alden SM. Morphine cholescintigraphy. Surg Gynecol Obstet 1990; 171: 227-32.
  1. Choy D, Shi EC, McLean RG, et al. Cholescintigraphy in acute cholecystitis, use of intravenous morphine. Radiology 1984; 151: 302-7.
  1. Fig LM, Wahl RL, Stewino RE, et al. Morphine-augmented hepatobiliary scintigraphy in the severely ill: caution is in order. Radiology 1990; 175: 467-73.
  1. Kim EE, Pjura G, Lowry P, et al. Morphine-augmented cholescintigraphy in the diagnosis of acute cholecystitis. Am J Roentgenol 1986; 147(6): 1177-9.
  1. Taylor A, Kipper MS, Witztum K, et al. Abnormal Tc-99m-PIPIDA scans mistaken for common bile duct obstruction. Radiology 1982; 144: 373-5.
  1. Szlabick RE, Catto JA, Fink-Bennett D, et al. Hepatobiliary scanning in the diagnosis of acute cholecystitis. Arch Surg 1980; 115(4): 540-4.
  1. Swayne LC. Acute acalculous cholecystitis: sensitivity in detection using technetium-99m iminodiacetic acid cholescintigraphy. Radiology 1986; 160(1): 33-8.
  1. Cawthon MA, Brown DM, Hartshorne MF, et al. Biliary scintigraphy. The ``hot rim'' sing. Clin Nucl Med 1984; 9(11): 619-21.
  1. Weissmann HS, Badia J, Sugarman LA, et al. Spectrum of 99m-Tc-IDA cholescintigraphic patterns in acute cholecystitis. Radiology 1981; 138(1): 167-75.
  1. Fink-Bennett D. Augmented cholescintigraphy: its role in detecting acute and chronic disorders of the hepatobiliary tree. Semin Nucl Med 1991; 21(2): 128-39.
  1. Krishnamurthy GT, Turner FE. Pharmacokinetics and clinical application of technetium 99m-labeled hepatobiliary agents. Semin Nucl Med 1990; 20(2): 130-49.
  1. Pediatric dosages recommended by USP Radiopharmaceuticals Advisory Panelists as of 08/92.
  1. Reviewers' comments per monograph revision of 11/03/92.
  1. Jaw TS, Wu C, Ho YH, et al. Diagnosis of obstructive jaundice in infants: Tc 99m DISIDA in duodenal juice. J Nucl Med 1984; 25: 360-3.
  1. Kirks DR, Coleman RE, Filston HC, et al. An imaging approach to persistent neonatal jaundice. Am J Radiol 1984; 142: 461-5.
  1. Majd M, Reba RC, Altman RP. Effect of phenobarbital on Tc 99m-IDA scintigraphy in the evaluation of neonatal jaundice. Semin Nucl Med 1981; 11: 194-204.
  1. Sty JS, Starshak RJ, Miller JH. Gastrointestinal nuclear medicine, in Baum S [editor]. Pediatric nuclear medicine. Norwalk, CT: Appleton-Century-Crofts: 53-83.
  1. Laven DL, Clanton JA, Hladik WB, et al. Pharmacologic alterations in the biorouting/performance of radiopharmaceuticals used in nuclear medicine adrenal, cerebral, hepatobiliary, pulmonary and renal scintigraphic studies. Bay Pines, FL: Gammascan Consultants: 25-8.
  1. Swayne LC, Kolc J. Erythromycin hepatotoxicity: a rare cause of a false-positive technetium-99m Disida study. Clin Nucl Med 1986; 11(1): 10-2.
  1. Hepatobiliary imaging protocol as of 03/91 sent by panelist.
  1. Oates E, Achong DM. Incidence and significance of enterogastric reflux during morphine-augmented cholescintigraphy. Clin Nucl Med 1992; 17(12): 926-8.
  1. Yeo EE, Low JC, Azizi F. False-negative morphine-augmented cholescintigraphy in a patient with gangrenous cholecystitis. Clin Nucl Med 1992; 17(12): 929-30.
  1. Bourekas EC, Tupler RH, Turbiner EH. Morphine-augmented cholescintigraphy with a false-negative result and an apparent ectopic gallbladder. Clin Nucl Med 1992; 17(12): 931-2.
  1. Reviewers' responses to Ballot of 5/11/94.
  1. Cherver LR, Nunn AD, Loberg MD. Radiopharmaceuticals for hepatobiliary imaging. Semin Nucl Med 1982; 12(1): 5-17.
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