Technetium Tc 99m Tetrofosmin (Systemic)
VA CLASSIFICATION
Primary: DX201
Commonly used brand name(s): Myoview.
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) or
Myocardial perfusion imaging, radionuclide—Technetium Tc 99m tetrofosmin is indicated in myocardial perfusion imaging to distinguish regions of reversible myocardial ischemia in the presence or absence of infarcted myocardium, following separate administration under stress and rest conditions {01} {02} {04} {05} {07} {08} {09} {10} {11} {12} {15} {17} {19} {20} {21}.
Physical Properties
Nuclear data
{01}| Radionuclide (half-life) |
Decay constant |
Mode of decay |
Principal photon emissions (keV) |
Mean number of photons/ disintegration (³0.01) |
| Tc 99m (6 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 tetrofosmin by myocardial tissue are not well established {01}. Technetium Tc 99m tetrofosmin is a lipophilic cationic agent (diphosphine group) {01} {02} {04} {09} {14}. The myocardial uptake of technetium Tc 99m tetrofosmin appears to occur by a passive diffusion process. When injected at rest, technetium Tc 99m tetrofosmin appears to accumulate in viable myocardial tissue; infarcts are thus delineated as areas that lack accumulation {09} {10} {11}. When injected at stress, technetium Tc 99m tetrofosmin accumulates in viable myocardial tissue in relation to myocardial blood flow {09}; thus, ischemic areas (e.g., those supplied by stenotic vessels) are detectable as areas of less accumulation {10} {11} {17}.
Distribution:
Technetium Tc 99m tetrofosmin is rapidly cleared from the blood after intravenous administration (< 5% of administered activity remains in blood by 10 minutes postinjection), accumulating in myocardium, skeletal muscle, liver, spleen, and kidneys in proportion to the regional perfusion {01} {02} {04} {09} {11} {17}. Uptake in myocardium is approximately 1.2% of the administered activity 5 minutes after injection, and approximately 1% at 2 hours {01} {04} {09}. Once technetium Tc 99m tetrofosmin is taken up by the myocardium, there is no, or minimal, redistribution over the following 3 to 4 hours {02} {04} {05} {07} {09} {15}. Washout from the myocardium is slow (4% of myocardial activity per hour postexercise) {05} {07} {17}.
Following injection at peak exercise, activity in the liver is lower than that in the heart as early as 5 minutes postinjection, with further decline over time (< 4.5% by 60 minutes) {02} {04} {11} {12} {15}. The gallbladder shows slightly higher activity than the heart in the first 15 minutes {02}.
Sequestration of activity by skeletal muscle is enhanced during exercise (probably due to a relative increase in the blood flow to skeletal tissue), but significantly reduced in all other organ systems {04} {17}.
Time to radioactivity visualization
Imaging is generally performed at 15 minutes after injection during stress, and at 30 to 60 minutes after injection during rest (delay allows for hepatic clearance) {01} {02} {04} {05} {11} {17}. Imaging is possible for up to 4 hours due to the slow washout of technetium Tc 99m tetrofosmin from myocardium {05}.
Note: Heart-to-liver activity ratios may be dependent on the applied stress condition (e.g., exercise vs. dipyridamole injection). Higher heart-to-liver ratios occur with exercise than with dipyridamole stress {12}.
Radiation dosimetry:
{01}
| Organ |
Estimated absorbed radiation dose * |
|||
|---|---|---|---|---|
| With exercise |
At rest |
|||
| mGy/ MBq |
rad/ mCi |
mGy/ MBq |
rad/ mCi |
|
| Gallbladder wall |
0.027 |
0.1 |
0.036 |
0.13 |
| Large intestine (upper) |
0.02 |
0.075 |
0.027 |
0.1 |
| Large intestine (lower) |
0.015 |
0.057 |
0.02 |
0.075 |
| Bladder wall |
0.014 |
0.052 |
0.017 |
0.063 |
| Small intestine |
0.012 |
0.045 |
0.015 |
0.057 |
| Ovaries |
0.0077 |
0.029 |
0.0088 |
0.033 |
| Uterus |
0.0071 |
0.026 |
0.0078 |
0.029 |
| Bone surfaces |
0.0062 |
0.023 |
0.0056 |
0.021 |
| Heart wall |
0.0051 |
0.019 |
0.0046 |
0.017 |
| Pancreas |
0.0047 |
0.017 |
0.0045 |
0.017 |
| Thyroid |
0.0047 |
0.017 |
0.0055 |
0.02 |
| Stomach |
0.0044 |
0.016 |
0.0044 |
0.016 |
| Kidneys |
0.0042 |
0.016 |
0.0041 |
0.015 |
| Adrenal glands |
0.004 |
0.015 |
0.0037 |
0.014 |
| Red bone marrow |
0.0038 |
0.014 |
0.0036 |
0.013 |
| Spleen |
0.0038 |
0.014 |
0.0034 |
0.013 |
| Muscle |
0.0034 |
0.013 |
0.0032 |
0.012 |
| Testes |
0.0033 |
0.012 |
0.003 |
0.011 |
| Thymus |
0.0032 |
0.012 |
0.0027 |
0.01 |
| Liver |
0.0031 |
0.012 |
0.0037 |
0.014 |
| Lungs |
0.0032 |
0.012 |
0.0027 |
0.01 |
| Brain |
0.0027 |
0.01 |
0.0022 |
0.008 |
| Breasts |
0.0023 |
0.008 |
0.0019 |
0.007 |
| Skin |
0.0022 |
0.008 |
0.0019 |
0.007 |
| Total body |
0.0037 |
0.014 |
0.0036 |
0.013 |
| Radionuclide |
Effective dose * |
|||
| With exercise |
At rest |
|||
| mSv/ MBq |
rem/ mCi |
mSv/ MBq |
rem/ mCi |
|
| Tc 99m |
0.0071 |
0.026 |
0.0082 |
0.03 |
Elimination
Within 48 hours—
Renal, approximately 40% of the administered activity under both rest and exercise conditions {01} {04}.
Fecal, approximately 26 to 41% (mean, 34%) of the administered activity at rest {01} {04} {14}, and approximately 17 to 34% (mean, 25%) after exercise {04} {17}.
Precautions to Consider
Carcinogenicity
Long-term animal studies to evaluate carcinogenic potential of technetium Tc 99m tetrofosmin have not been performed {01}.
Mutagenicity
Tetrofosmin has not been shown to be mutagenic in vitro in the Ames test, mouse lymphoma and human lymphocyte tests, and in in vivo mouse micronucleus assay {01} {04} {06} {08} {17}.
Pregnancy/Reproduction
Pregnancy—
Tc 99m (as free pertechnetate) crosses the placenta. However, studies to assess transplacental transfer of technetium Tc 99m tetrofosmin have not been done in humans {01}.
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 practical amount {03}.
Studies have not been done in animals {01}.
FDA Pregnancy Category C {01}.
Breast-feeding
Although it is not known whether technetium Tc 99m tetrofosmin is distributed into breast milk, it is known that Tc 99m as free pertechnetate is distributed into breast milk {01}. To avoid radiation exposure to the infant, discontinuation of nursing for a period of 24 hours is recommended after administration of technetium Tc 99m–labeled radiopharmaceuticals {03} {17}.
Pediatrics
Although technetium Tc 99m tetrofosmin is used in children, there have been no specific studies evaluating safety and efficacy {01}.
Geriatrics
Appropriate studies on the relationship of age to the effects of technetium Tc 99m tetrofosmin have not been performed in the geriatric population. However, clinical trials and studies that included older patients were conducted {01} {02} {07} {08} {09} {10} {12} {13}, and geriatrics-specific problems that would limit the usefulness of this agent in the elderly are not expected {01} {07} {08} {09} {10} {11}.
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{01}
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
Incidence rare
Allergic reaction {01}(skin rash; troubled breathing)
angina{01} (chest pain)
hypertension{01}
Those indicating need for medical attention only if they continue or are bothersome
Incidence less frequent or rare
Burning sensation in hard palate{01}{09}
gastrointestinal symptoms{01}{04} (abdominal or stomach discomfort; vomiting)
hypotension{01} (lightheadedness; dizziness)
metallic taste{01}{04}
unusual smell{01}{09}
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 received is 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 tetrofosmin 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 at least 2 hours before the exercise test
Other special preparatory instructions may also be given; patient should inquire in advance
Precautions after having this test
Adequate intake of fluids and voiding as often as possible after examination to minimize radiation exposure to bladder
Side/adverse effects
Signs of potential side effects, especially allergic reaction, angina, and hypertension
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 {02} {04} is usually recommended, or at least 2 hours should elapse after a light breakfast, before the exercise test {02}.
Adequate hydration of the patient is recommended before and after examination to promote urinary flow. Also, urination is recommended as often as possible after the examination to reduce bladder exposure to radiation {01}.
For exercise studies, imaging may be started as early as 5 minutes after injection of technetium Tc 99m tetrofosmin {02} {04}, with imaging generally performed at 15 minutes {01} {02} {04} {17}. For rest imaging, a delay of 30 minutes is needed in most patients after the administration of technetium Tc 99m tetrofosmin to allow clearance of the tracer from the liver {02}.
Safety considerations for handling this radiopharmaceutical
Guidelines for the receipt, storage, handling, dispensing, and disposal of radioactive materials are available from scientific, professional, state, federal, and international bodies. Handling of this radiopharmaceutical should be limited to those individuals who are appropriately qualified and authorized {16}.
Parenteral Dosage Forms
TECHNETIUM Tc 99m TETROFOSMIN INJECTION
Usual adult and adolescent administered activity
Cardiac imaging
Intravenous, 185 to 296 megabecquerels (5 to 8 millicuries) administered at peak exercise; then 555 to 888 megabecquerels (15 to 24 millicuries) administered 4 hours later, at rest {01} {02} {07}.
Note: A two-day protocol has been found to increase image quality. According to this protocol, the rest and stress imaging studies are performed on two separate days; patients receive 500 megabecquerels (14 millicuries) of technetium Tc 99m tetrofosmin on each day {17} {22}.
Also, a combined myocardial imaging protocol involving thallous chloride Tl 201 scintigraphy at rest followed by technetium Tc 99m tetrofosmin imaging after stress is being used {17}. It involves the intravenous administration at rest of 74 megabecquerels (2 millicuries) of thallous chloride Tl 201, with imaging performed 20 minutes postinjection, followed by the administration of 370 megabecquerels (10 millicuries) of technetium Tc 99m tetrofosmin at 4 minutes of exercise, with imaging performed 20 minutes after the completion of the stress test {17} {23}. This combined thallium/tetrofosmin protocol requires a total time of 90 minutes {23}.
Usual pediatric administered activity
Minimum dosage has not been established {01}.
Usual geriatric administered activity
See Usual adult and adolescent administered activity.
Strength(s) usually available
U.S.—
0.23 mg tetrofosmin, 0.03 mg stannous chloride dihydrate, 0.32 mg disodium sulfosalicylate, 1 mg sodium D-gluconate, and 1.8 mg sodium hydrogen carbonate in lyophilized form under nitrogen atmosphere, per vial (Rx) [Myoview{01}]
Canada—
Not commercially available.
Packaging and storage:
Store between 2 and 25 °C (36 and 77 °F), unless otherwise specified by manufacturer. Protect from freezing {01}.
Note: Before radiolabeling, the kit must be stored between 2 and 8 °C (36 and 46 °F), and protected from light {01}.
Preparation of dosage form:
To prepare technetium Tc 99m tetrofosmin injection, an oxidant-free sodium pertechnetate Tc 99m solution is used {01}.
Preparation of technetium Tc 99m tetrofosmin injection does not require heating. Instead, a 15-minute incubation period at room temperature is sufficient after radiolabeling {01} {07} {08}.
See manufacturer's package insert for complete instructions {01}.
Stability:
Product is stable (> 90% radiochemical purity is maintained for 8 hours after reconstitution) {04}. Package insert states that injection should be administered within 8 hours after preparation since it does not contain a preservative {01} {04} {06}.
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 {01}. Final preparation should appear clear and free of particulate matter {01}.
Note: Caution—Radioactive material.
Developed: 12/04/1996
References
- Myoview package insert (Amersham—US), Rec 4/96.
- Jain D, Wackers F, Mattera J, et al. Biokinetics of technetium-99m-tetrofosmin: myocardial perfusion imaging agent: implications for a one-day imaging protocol. J Nucl Med 1993; 34: 1254-9.
- Radiopharmaceuticals Advisory Panel meeting, 5/8/91.
- Higley B, Smith FW, Smith T, et al. Technetium-99m-1,2-[bis(2–ethoxyethyl)phosphino]-ethane: human biodistribution, dosimetry and safety of a new myocardial perfusion imaging agent. J Nucl Med 1993; 34(1): 30-8.
- Sridhara BS, Braat S, Rigo P, et al. Comparison of myocardial perfusion imaging with technetium-99m tetrofosmin versus thallium-201 in coronary artery disease. Am J Cardiol 1993; 72: 1015-9.
- Kelly JD, Forster AM, Higley B, et al. Technetium-99m-tetrofosmin as a new radiopharmaceutical for myocardial perfusion imaging. J Nucl Med 1993; 34(2): 222-7.
- Rigo P, Leclercq B, Itti R, et al. Technetium-99m-tetrofosmin myocardial imaging: a comparison with thallium-201 and angiography. J Nucl Med 1994; 35(4): 587-93.
- Tamaki N, Takahashi N, Kawamoto M, et al. Myocardial tomography using technetium-99m-tetrofosmin to evaluate coronary artery disease. J Nucl Med 1994; 35(4): 594-600.
- Zaret BL, Rigo P, Wackers FJT, et al. Myocardial perfusion imaging with 99mTc tetrofosmin. Circulation 1995; 91(2): 313-9.
- Matsunari I, Fujino S, Taki J, et al. Myocardial viability assessment with technetium-99m-tetrofosmin and thallium-201 reinjection in coronary artery disease. J Nucl Med 1995; 36(11): 1961-7.
- Cuocolo A, Soricelli A, Nicolai E, et al. Technetium-99m-tetrofosmin regional myocardial uptake at rest: relation to severity of coronary artery stenosis in previous myocardial infarction. J Nucl Med 1995; 36(6): 907-13.
- Flamen P, Bossuyt A, Franken PR. Technetium-99m-tetrofosmin in dipyridamole-stress myocardial SPECT imaging: intraindividual comparison with technetium-99m-sestamibi. J Nucl Med 1995; 36(11): 2009-15.
- Matsunari I, Fujino S, Taki J, et al. Comparison of defect size between thallium-201 and technetium-99m-tetrofosmin myocardial single-photon emission computed tomography in patients with single-vessel coronary artery disease. Am J Cardiol 1996 Feb; 77: 350-4.
- Taillefer R. New agents and future use of myocardial perfusion imaging. Presented: Society of Nuclear Medicine 43rd Annual Meeting; 1996 Jun; Denver, CO.
- Nakajima K, Taki J, Shuke N, et al. Myocardial perfusion imaging and dynamic analysis with technetium-99m-tetrofosmin. J Nucl Med 1993; 34(9): 1478-84.
- Radiopharmaceuticals Advisory Panel meeting, 4/96.
- Reviewers' comments on monograph revision of 12/4/96.
- Radiopharmaceutical Internal Dose Information Center, August 1996. Oak Ridge Institute for Science and Education.
- Cuocolo A, Nicolai E, Soricelli A, et al. Technetium 99m-labeled tetrofosmin myocardial tomography in patients with coronary artery disease: comparison between adenosine and dynamic exercise stress testing. J Nucl Cardiol 1996; 3(3): 194-203.
- Fukuzawa S, Ozawa S, Inagaki M, et al. Tc-99m tetrofosmin myocardial perfusion SPECT after dipyridamole combined with low-level exercise in the diagnosis of coronary artery disease. Ann Nucl Med 1996; 10(2): 231-5.
- He ZX, Iskandrian AS, Gupta NC, et al. Assessing coronary artery disease with dipyridamole technetium-99m-tetrofosmin SPECT: a multicenter trial. J Nucl Med 1997; 38(1): 44-8.
- van Eck-Smit BL, Poots S, Zwinderman AH, et al. Myocardial SPECT imaging with Tc-99m tetrofosmin in clinical practice: comparison of a 1 day and a 2 day imaging protocol. Nucl Med Commun 1997; 18(1): 24-30.
- Mahmood S, Gunning M, Bomanji JB, et al. Combined rest thallium-201/stress technetium-99m-tetrofosmin SPECT: feasibility and diagnostic accuracy of a 90–minute protocol. J Nucl Med 1995; 36(6): 932-5.
