Technetium Tc 99m Teboroxime (Systemic)


VA CLASSIFICATION
Primary: DX201

Commonly used brand name(s): CardioTec.

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 (cardiac disease)—

Indications

Accepted

Cardiac imaging, radionuclide
Myocardial infarction (diagnosis) and
Myocardial perfusion imaging, radionuclide—Technetium Tc 99m teboroxime is indicated in myocardial perfusion imaging to distinguish normal from abnormal myocardium in patients with suspected coronary artery disease (CAD) using rest and stress techniques. {01} {11} {12} {13} {14} {15} {19} {20} {21} {24} {25} {28} {29} {30} {31} {33}


Physical Properties

Nuclear data:



Radionuclide
(half-life)
Decay
constant
Mode
of
decay
Principal
photon
emissions
(keV)
Mean
number of
photons/
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

Mechanism of action/Effect:

The mechanisms for uptake and retention of technetium Tc 99m teboroxime by myocardial tissue are not well established. Unlike cationic thallous chloride Tl 201 and technetium Tc 99m sestamibi, technetium Tc 99m teboroxime has a neutral charge. Because of its neutral charge and high lipophilicity, the myocardial uptake of technetium Tc 99m teboroxime appears to occur by a passive diffusion process. The rate of passive uptake is determined by the membrane permeability of the drug, the surface area of the vascular beds to which it is exposed, the vascular and extravascular concentrations of the drug, and the rate of delivery of the drug. {38} While technetium Tc 99m teboroxime's mechanism of myocardial retention is less efficient than that of thallous chloride Tl 201 or technetium Tc 99m sestamibi, its myocardial extraction is higher. Its rapid myocardial washout allows early repeat studies following the application of a pharmacologic or physical intervention. {08} {09} {11} {12} {13} {16} {17} {23} {29} {30} {31}

Distribution:

Technetium Tc 99m teboroxime is rapidly cleared from blood after intravenous administration, with high myocardial extraction in proportion to myocardial perfusion even at extremely high flow rates. Myocardial uptake is apparent scintigraphically at 1 minute after injection. A significant amount of the initial myocardial activity is cleared by 20 to 30 minutes after administration. {01} {06} {07} {08} {10} {11} {16} {17} {30} {31} {33}

Liver uptake of technetium Tc 99m teboroxime becomes significant by 5 to 10 minutes after injection and has a slow clearance (half-life approximately 1.5 hours) that can impair visualization of the inferior left ventricular wall. {01} {06} {07} {08} {10} {17} {20} {28} {30} {31}

There is marked first-pass uptake of technetium Tc 99m teboroxime in the lungs with rapid subsequent clearance within the first 2 minutes after injection. This initial lung uptake may complicate first-pass radionuclide angiography image interpretation, since it results in lower ejection fractions, higher pulmonary transit times, higher calculated pulmonary blood volume indices, and poorer left ventricular border definition. {26} {38}

Protein binding:

Very low (<10%). {01} {23} {32}

Half-life:

Elimination (myocardium)—10 to 15 minutes. {08}

Note: A biexponential pattern of myocardial washout has been demonstrated in animals and man. About two-thirds of myocardial activity demonstrates an effective half-life of 5.2 minutes; the remaining one-third demonstrates an effective half-life of 3.8 hours. {10} {20} {24} {30} {38} At 10 minutes after injection, approximately 10.4±4.4% (mean) of the injected dose remains in the circulation. {01} {06} {07} {08} {10} {11} {16} {17} {30} {31} {33} {38}


Radiation dosimetry:
{01}{22}{38}

Mode of
administra-
tion
Estimated absorbed radiation dose*
Target organ
mGy/MBq
rad/mCi
Intravenous
Large intes-
tine, upper
0.033
0.12
Gallbladder wall
0.026
0.097
Large intestine,
lower
0.023
0.087
Small intestine
0.018
0.067
Liver
0.017
0.062
Ovaries
0.0098
0.036
Lungs
0.0076
0.028
Urinary bladder
wall
0.0074
0.027
Heart wall
0.0055
0.020
Kidneys
0.0055
0.020
Red marrow
0.0045
0.017
Spleen
0.0040
0.015
Brain
0.0034
0.012
Thyroid
0.0029
0.011
Testes
0.0028
0.010
Total body
0.0045
0.017
Effective dose: 0.013 mSv/MBq (0.048 rem/mCi) {17} {22}
* Assuming 6-hour gallbladder emptying; 2-hour urinary bladder void. {01} {22}

Elimination:
    Hepatobiliary, mainly. Renal, 22±13% in 24 hours. {01} {02}


Precautions to Consider

Carcinogenicity

Long-term animal studies to evaluate carcinogenic potential of technetium Tc 99m teboroxime have not been performed. {33}

Mutagenicity

Decayed technetium Tc 99m teboroxime has not been shown to be mutagenic in a reversion test with bacteria, a chromosomal aberration assay, and an in vivo mouse micronucleus assay. {01} {33}

At high concentrations that were toxic to the cells and reduced growth to 33% or less relative to vehicle controls, technetium Tc 99m teboroxime was weakly positive for inducing forward mutations at the TK locus in L5178Y mouse lymphoma cells without metabolic activation. In the presence of metabolic activation, technetium Tc 99m teboroxime gave negative results in this assay. {01} {33}

Pregnancy/Reproduction

Pregnancy—
Tc 99m (as free pertechnetate) crosses the placenta. However, studies with technetium Tc 99m teboroxime have not been done in humans.

The possibility of pregnancy should be assessed in women of child-bearing potential. Clinical situations exist in which the benefit to the patient and fetus from information derived from radiopharmaceutical use outweighs the risks from fetal exposure to radiation. In these situations, the physician should use discretion and reduce the administered activity of the radiopharmaceutical to the lowest possible amount. {05}

Studies have not been done in animals. {01}

FDA Pregnancy Category C. {01} {33}

Breast-feeding

Although it is not known whether technetium Tc 99m teboroxime is distributed into breast milk, it is known that Tc 99m as free pertechnetate is distributed into breast milk. Because of the potential risk to the infant from radiation exposure, discontinuation of nursing for a period of 24 hours is recommended after administration of technetium Tc 99m–labeled radiopharmaceuticals. {01} {05}

Pediatrics

Although technetium Tc 99m teboroxime is used in children, there have been no specific studies evaluating safety and efficacy. When used in children, the diagnostic benefit should be judged to outweigh the potential risk of radiation. {01} {05}


Geriatrics


Appropriate studies on the relationship of age to the effects of technetium Tc 99m teboroxime have not been performed in the geriatric population. However, clinical trials and studies were conducted including older patients and geriatrics-specific problems that would limit the usefulness of this agent in the elderly are not expected. {02} {30}

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).


Risk-benefit should be considered when the following medical problem exists
Sensitivity to the radiopharmaceutical preparation


Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention only if they continue or are bothersome
Incidence less frequent or rare {01} {33}
    
Burning sensation at injection site
    
hypotension
    
metallic taste
    
nausea
    
numbness of hand and arm
    
swelling of face





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: Accumulation of radioactivity in myocardial cells as a function of relative blood flow

Differences in uptake of radioactivity can be visualized

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

Before having this test
»   Conditions affecting use, especially:
Sensitivity 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 study should be considered





Breast-feeding—Not known if technetium Tc 99m teboroxime is distributed into breast milk, but Tc 99m as free pertechnetate is distributed into breast milk; temporary discontinuation of nursing is recommended to avoid any unnecessary absorbed radiation dose to the infant

Preparation for this test
Fasting for 4 to 8 hours before the stress/rest test

Other special preparatory instructions may also be given; patient should inquire in advance


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 licensed by the Nuclear Regulatory Commission (NRC) or the appropriate Agreement State agency, if required, or, outside the U.S., the appropriate authority.

Fasting is usually recommended for 4 to 8 hours before the stress/rest test. {21} {38}

Technical factors such as tomographic reconstruction artifacts, patient movement, diaphragmatic attenuation, and breast attenuation in female patients may cause false-positive results (false perfusion defects). {16} {38}

In conjunction with exercise or pharmacologic vasodilatation stress testing, technetium Tc 99m teboroxime should be administered at the inception of a period of maximum stress that is continued for approximately 30 to 60 seconds after injection. {01} {11} {20} {31} {32} {38}

High liver extraction of technetium Tc 99m teboroxime may interfere with visualization of the inferior wall of the heart. Positioning the patient upright during image acquisition is helpful in minimizing the contribution of liver activity, since in the upright position the liver tends to drop downward, allowing better separation of the cardiac and hepatic activities. {11} {15} {20} {21}

For either rest or stress studies, imaging must begin within 2 to 5 minutes after injection of technetium Tc 99m teboroxime and must be completed within 5 to 10 minutes. After 5 minutes, differential washout of technetium Tc 99m teboroxime begins to introduce artifacts. If image acquisition takes too long, perfusion defects can become less apparent before acquisition is complete, resulting in an underestimation of the number and severity of ischemic segments. A significant amount of the initial myocardial activity is cleared by 20 to 30 minutes after administration. {01} {11} {30} {31} {38}

Rapid myocardial washout and early hepatic uptake necessitates use of rapid imaging protocols, and may require a multiple-headed single-photon emission computed tomography (SPECT) camera to complete image acquisition in 3 to 4 minutes. {10} {17} {28} {30} {38}

For studies performed in conjunction with pharmacologic stress testing
Pharmacologic stress, induced by intravenous adenosine or dipyridamole, may be preferred for stress/rest studies using technetium Tc 99m teboroxime since the patient can be infused while in position under the camera, thus eliminating delays between tracer injection and the start of image acquisition. {28} {30}

Technetium Tc 99m teboroxime is usually administered during the third minute of the 4- to 5-minute infusion of adenosine, or 2 minutes after the 4-minute dipyridamole infusion. {24} {29} {30}

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. {18}


Parenteral Dosage Forms

TECHNETIUM Tc 99m TEBOROXIME INJECTION

Usual adult and adolescent administered activity
Cardiac imaging
Intravenous, 555 to 1110 megabecquerels (15 to 30 millicuries). {01}


Note: Due to the short residence time of technetium Tc 99m teboroxime in the myocardium, two separate injections are needed for a stress/rest perfusion study. {11}
When a stress study is to be performed prior to a rest study, it is recommended that an interval of 11/2 hours be allowed for the effects of exercise to dissipate. {01} {11} {12}
For same-day rest/stress studies, a combined dose of 1295 to 1850 megabecquerels (35 to 50 millicuries) is used. {01}
When a rest study is to be performed prior to a stress study, it is only necessary to wait until the residual myocardial activity clears. In most cases, the stress study may be performed in one hour. {01} {11}


Usual pediatric administered activity
Minimum dosage has not been established. {05}

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

Strength(s) usually available
U.S.—


2 mg of cyclohexanedione dioxime, 2 mg of methyl boronic acid, 2 mg pentetic acid, 9 mg citric acid (anhydrous), 100 mg sodium chloride, 50 mg gamma cyclodextrin, and 50 mcg stannous chloride (anhydrous) in lyophilized form under nitrogen atmosphere, per 5-mL reaction vial (Rx) [CardioTec]

Note: Technetium Tc 99m teboroxime is a boronic acid technetium dioxime (BATO) derivative. {01} {08} {10} {11} {12}


Canada—
Not commercially available. {03}

Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Protect from freezing. {01}

Note: Before radiolabeling, the kit is also stored at room temperature. {01}


Preparation of dosage form:
To prepare technetium Tc 99m teboroxime injection, an oxidant-free sodium pertechnetate Tc 99m solution is used.

During reconstitution, it is important that air is not added to the nitrogen atmosphere of the vial, since air will cause oxidation, thus decreasing the radiochemical purity of the compound. {11}

See manufacturer's package insert for complete instructions. {01}

Stability:
Product is stable (24-month shelf life before radiolabeling); U.S. package insert states that injection should be administered within 6 hours after preparation since it does not contain a preservative. {01} {05} {07} {31}

Incompatibilities:
If oxidants such as peroxides and hypochlorites are present in the sodium pertechnetate Tc 99m used for labeling, the final preparation may be adversely affected and should be discarded. Final preparation should appear clear to slightly opalescent and free of particulate matter and discoloration. {01} {10}

Note: Caution—Radioactive material.




Revised: 05/18/1995



References
  1. CardioTec package insert (Squibb—US), Rev 12/90.
  1. Squibb presentation at FDA on 11/17/90.
  1. Personal communication, Canada Squibb Diagnostics 8/91.
  1. Reviewers' comments on Technetium Tc 99m Sestamibi monograph.
  1. Radiopharmaceuticals Advisory Panel meeting, 05/08/91.
  1. Berman DS. Introduction—Technetium 99m myocardial perfusion imaging agents and their relation to thallium-201. Am J Cardiol 1990; 66(13): 1E-4E.
  1. Meerdink DJ, Leppo JA. Experimental studies of the physiologic properties of technetium-99m agents: myocardial transport of perfusion imaging agents. Am J Cardiol 1990; 66(13): 9E-15E.
  1. Berman DS, Kiat H, Van Train KF, et al. Comparison of SPECT using technetium-99m agents and thallium-201 and PET for the assessment of myocardial perfusion and viability. Am J Cardiol 1990; 66(13): 72E-79E.
  1. Stewart RE, Chiao PC, Roger WL, et al. Assessment of myocardial blood flow by SPECT based on clearance kinetics of the new technetium labeled flow tracer SQ30217 [abstract]. Circulation 1989; 80: 618.
  1. Johnson LL, Seldin DW. Clinical experience with technetium-99m teboroxime, a neutral, lipophilic myocardial perfusion imaging agent. Am J Cardiol 1990; 66: 63E-67E.
  1. McSherry BA. Technetium-99m-Teboroxime: a new agent for myocardial perfusion imaging. J Nucl Med Technol 1991; 19(1): 22-6.
  1. Seldin DW, Johnson LL, Blood DK, et al. Myocardial perfusion imaging with technetium-99m SQ30217: comparison with thallium-201 and coronary anatomy. J Nucl Med 1989: 30(3): 312-9.
  1. Stewart RE, Schwaiger M, Hutchins GD, et al. Myocardial clearance kinetics of technetium-99m-SQ30217: a marker of regional myocardial blood flow. J Nucl Med 1990; 31(7): 1183-90.
  1. Li Q-S, Solot G, Frank TL, et al. Tomographic myocardial perfusion imaging with technetium-99m-teboroxime at rest and after dipyridamole. J Nucl Med 1991; 32(10): 1968-76.
  1. Hendel RC, McSherry B, Karimeddini M, et al. Diagnostic value of a new myocardial perfusion agent, teboroxime (SQ30217), utilizing a rapid planar imaging protocol: preliminary results. J Am Coll Cardiol 1990; 16(6): 855-61.
  1. Marshall RC, Leidholdt EM Jr, Zhang D-Y, et al. The effect of flow on technetium-99m-teboroxime (SQ30217) and thallium-201 extraction and retention in rabbit heart. J Nucl Med 1991; 32(10): 1979-88.
  1. Reviewer's comment, 09/91.
  1. Reviewers' responses to Ballot of 5/11/94.
  1. Stewart RE, Heyl B, O'Rourke RA, et al. Demonstration of differential post-stenotic myocardial technetium-99m-teboroxime clearance kinetics after experimental ischemia and hyperemic stress. J Nucl Med 1991; 32(10): 2000-8.
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    1. CardioTec package insert (Squibb—US), Rev 1/91.
    1. Hockings B, Saltissi S, Croft DN, et al. Effect of beta adrenergic blockade of thallium-201 myocardial perfusion images. Br Heart J 1983; 49: 83-9.
    1. Ponto JA, Holmes KA. Discontinuation of beta blockers before exercise radionuclide ventriculograms. J Nucl Med 1982; 23: 456-7.
    1. Osbakken MD, Okada RD, Boucher CA, et al. The effect of Inderal, exercise level, and subcritical disease on the specificity of exercise thallium-201 imaging. J Nucl Med 1981; 22: 41.
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    1. Reviewer's comment, 10/18/94.
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