Technetium Tc 99m Pyrophosphate (Systemic)


VA CLASSIFICATION
Primary: DX201

Commonly used brand name(s): MPI Pyrophosphate; Phosphotec; TechneScan PYP.

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 (bone disease; cardiac disease; gastrointestinal bleeding [without Tc 99m label])—

Indications

Accepted

—For technetium Tc 99m pyrophosphate

Skeletal imaging, radionuclide—Technetium Tc 99m pyrophosphate is indicated as a skeletal imaging agent to delineate areas of altered osteogenesis, such as those that occur with metastatic bone disease, Paget's disease, arthritic disease, osteomyelitis, and fractures. {01} {14} {15}

Cardiac imaging, radionuclide—Technetium Tc 99m pyrophosphate is indicated as a cardiac imaging agent to aid in the diagnosis of acute myocardial infarction. {01} {08} {14} {15}

—For sodium pyrophosphate without Tc 99m label

Red blood cells, labeling of—Intravenous injection of the unlabeled sodium pyrophosphate and stannous chloride complex, when followed by the injection of sodium pertechnetate Tc 99m, is indicated for in vivo or modified in vitro/in vivo labeling of red blood cells. Red blood cells labeled with sodium pertechnetate Tc 99m are used for blood pool imaging in the following diagnostic study:
Cardiac blood pool imaging, radionuclide—To detect pericardial effusion, intracardiac abnormalities, or ventricular aneurysms. {01} {14}

Bleeding, gastrointestinal (diagnosis)—To detect the site of bleeding in patients suspected of gastrointestinal bleeding. {01} {14}


Physical Properties

Nuclear data:



Radionuclide
(half-life)
Decay
constant
Mode
of
decay
Principal
photons
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—
    Sodium pyrophosphate: 265.90
    Stannous chloride: 225.63

Mechanism of action/Effect:

Skeletal and cardiac imaging—Exact mechanism is not known. It is generally accepted that technetium Tc 99m pyrophosphate localizes on the surface of hydroxyapatite crystals, found in bone and within infarcted myocardial cells, by a process termed chemisorption, with blood flow and/or blood concentration being most important in the delivery of the agent to sites of uptake. Visualization of osseous lesions is possible since skeletal uptake of technetium Tc 99m pyrophosphate is altered in areas of abnormal osteogenesis. {22}

Red blood cells, labeling of—When used for cardiac blood pool imaging or to detect gastrointestinal bleeding, pretreatment with the stannous ion-containing phosphate complex causes the technetium Tc 99m (as sodium pertechnetate Tc 99m) to bind to the red blood cells in vivo , with about 76% of the injected radioactivity remaining in the blood pool long enough to provide images of the cardiac chambers or sites of active (rapid) or cumulative (intermittent) gastrointestinal bleeding. Modified in vitro/in vivo method of labeling red blood cells usually results in a greater percent of the injected radioactivity remaining in the blood pool. {01} {11}

Distribution:

Selectively concentrated in areas of altered osteogenesis and injured myocardium with minimal uptake by soft-tissue organs. {01}

Radiation dosimetry:
{17}

Estimated absorbed radiation dose
for Technetium Tc 99m Pyrophosphate*
Organ
mGy/MBq
rad/mCi
Bone surfaces
0.063
0.23
Bladder wall
0.050
0.19
Red marrow
0.0096
0.036
Kidneys
0.0073
0.027
Uterus
0.0061
0.023
Large intestine
wall (lower)

0.0038

0.014
Ovaries
0.0035
0.013
Testes
0.0024
0.0089
Small intestine
0.0023
0.0085
Large intestine
wall (upper)

0.0020

0.0074
Adrenals
0.0019
0.0070
Pancreas
0.0016
0.0059
Spleen
0.0014
0.0052
Liver
0.0013
0.0048
Lungs
0.0013
0.0048
Stomach wall
0.0012
0.0044
Thyroid
0.0010
0.0037
Breast
0.00088
0.0033
Other tissue
0.0019
0.0070
Effective dose: 0.008 mSv/MBq (0.030 rem/mCi)


Estimated absorbed radiation dose
for Sodium Pertechnetate Tc 99m
Organ
mGy/MBq
rad/mCi
Stomach wall
0.029
0.11
Thyroid
0.023
0.085
Bladder wall
0.019
0.070
Small intestine
0.018
0.067
Ovaries
0.010
0.037
Salivary glands
0.0093
0.034
Uterus
0.0081
0.030
Large intestine
wall (upper)

0.062

0.23
Large intestine
wall (lower)

0.062

0.23
Red marrow
0.0061
0.022
Pancreas
0.0059
0.022
Kidneys
0.0050
0.019
Spleen
0.0044
0.016
Bone surfaces
0.0039
0.014
Liver
0.0039
0.014
Adrenals
0.0036
0.013
Lungs
0.0027
0.010
Testes
0.0027
0.010
Breast
0.0023
0.0085
Other tissue
0.0034
0.013
Effective dose: 0.013mSv/MBq (0.048 rem/mCi)
* For adults. Intravenous injection of technetium Tc 99m–labeled phosphates and phosphonates for skeletal and cardiac imaging.
 For adults. Intravenous injection of sodium pertechnetate Tc 99m preceded by intravenous administration of unlabeled sodium pyrophosphate for cardiac blood pool imaging. Without blocking agent.
 Data based on the International Commission on Radiological Protection (ICRP) Publication 53—Radiation dose to patients from radiopharmaceuticals. {17}

Elimination:
    Renal, 40% of the administered activity of technetium Tc 99m pyrophosphate eliminated within 24 hours. {01}


Precautions to Consider

Carcinogenicity/Mutagenicity

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

Pregnancy/Reproduction

Pregnancy—
Tc 99m (as free pertechnetate) crosses the placenta. Studies with technetium Tc 99m pyrophosphate have not been done 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 dose to the lowest possible amount. {18}

Studies have not been done in animals.

FDA Pregnancy Category C. {14} {15}

Breast-feeding

Although it is not known whether technetium Tc 99m pyrophosphate 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. 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}

Pediatrics

Diagnostic studies performed to date using technetium Tc 99m–labeled red blood cells have not demonstrated pediatrics-specific problems that would limit the usefulness of technetium Tc 99m pyrophosphate in children. However, there have been no specific studies evaluating the safety and efficacy of technetium Tc 99m pyrophosphate in pediatric patients. When this radiopharmaceutical is used in children, the diagnostic benefit should be judged to outweigh the potential risk of radiation. {05} {10} {18}


Geriatrics


Diagnostic studies performed to date using technetium Tc 99m pyrophosphate have not demonstrated geriatrics-specific problems that would limit the usefulness of technetium Tc 99m pyrophosphate in the elderly. {07}

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 skeletal imaging

Due to other medications
Amphotericin B or
Antineoplastics    (biodistribution of technetium Tc 99m pyrophosphate may be altered with concurrent administration of these medications {13})


Antacids, aluminum-containing    (high blood concentrations of aluminum ion, which may occur in patients with gastrointestinal obstruction or impaired renal function, may cause localization of technetium Tc 99m pyrophosphate in the liver and spleen {01} {05} {06} {13})


Diatrizoate sodium    (possible renal and hepatic uptake if diatrizoate sodium is administered intravenously immediately after technetium Tc 99m pyrophosphate {05} {13})


Etidronate    (etidronate may interfere with bone uptake of technetium Tc 99m pyrophosphate; discontinuation of etidronate therapy for a 2-week period before performance of a bone scan with technetium Tc 99m pyrophosphate is recommended {12} {20} {22})


Heparin calcium, subcutaneous or
Radiation therapy    (concurrent administration may result in extraosseous accumulation of technetium Tc 99m pyrophosphate {11})


Iron dextran, intramuscular or
Meperidine, intramuscular    (possible accumulation of technetium Tc 99m pyrophosphate at site of injection of these medications {05} {13})


Iron supplements or preparations    (iron overload may cause a decrease in bone uptake of technetium Tc 99m pyrophosphate {05} {13})


Potassium phosphates or
Potassium and sodium phosphates or
Sodium phosphates    (saturation of bone binding sites by phosphorous ions in these medications may cause decreased bone uptake of technetium Tc 99m pyrophosphate {05})


Due to medical problems or conditions
Amyloidosis or
Carcinomas or
Cirrhosis or
Diabetes mellitus or
Hypercalcemia    (biodistribution of technetium Tc 99m pyrophosphate may be altered, resulting in an increased uptake by other organs {13})


Blood transfusions, repeated    (may cause a decrease in bone uptake {13})


Bone demineralization, glucocorticoid-induced    (long-term therapy with glucocorticoids may induce bone mineral depletion, thus causing decreased bone uptake of technetium Tc 99m pyrophosphate {05})


Gynecomastia, estrogen-induced or
Lactation    (possible localization of technetium Tc 99m pyrophosphate in breast {05})


Obesity    (attenuation of photons coming from bone may decrease visualization )


Osteoporosis    (reduced mineral deposit in bone may result in images with lower target to non-target ratio)


Renal function impairment    (decreased drug clearance from blood and soft tissues may decrease visualization because of a lower bone to background ratio resulting from the increased circulating activity; also, chronic renal function impairment may cause metastatic calcification and altered biodistribution of technetium Tc 99m pyrophosphate)

With results of cardiac imaging

Due to other medications
Antacids, aluminum-containing    (high blood concentrations of aluminum ion, which may occur in patients with gastrointestinal obstruction or impaired renal function, may cause localization of technetium Tc 99m pyrophosphate in the liver and spleen {06})


Estrogens    (possible localization of technetium Tc 99m pyrophosphate in breast {06})


Heparin sodium    (diffuse uptake of technetium Tc 99m pyrophosphate into the myocardium, with signs of diminished uptake into the infarct {06})


Methylprednisolone    (methylprednisolone may increase glomerular filtration rate and excretion of technetium Tc 99m pyrophosphate, which results in faster blood clearance of the radiotracer, thus decreasing myocardial uptake of the radiotracer {06})


Radiation therapy    (diffuse myocardial uptake of technetium Tc 99m pyrophosphate {06} {13})


Verapamil    (patchy liver uptake of technetium Tc 99m pyrophosphate may result due to hepatocellular damage caused by verapamil toxicity {06})


Due to medical problems or conditions
Amyloidosis or
Hyperphosphatemia or
Sarcoidosis, myocardial    (diffuse cardiac uptake may occur {13})


Angina pectoris, unstable or
Cardiac contusions or
Coronary bypass surgery, recent or
Myocardial infarcts, previous    (false-positive cardiac images may occur {13})


Gynecomastia, estrogen-induced or
Lactation    (possible localization of technetium Tc 99m pyrophosphate in breast {13})


Myocardial infarcts, time of    (false-negative cardiac images may occur in the diagnosis of acute myocardial infarction if test is performed too early in the evolutionary phase or too late in the resolution phase of the infarct {01} {12})

With results of blood pool imaging (cardiac blood pool imaging and diagnosis of gastrointestinal bleeding)

Due to other medications
Digoxin or
Doxorubicin or
Heparin sodium or
Hydralazine or
Methyldopa or
Prazosin or
Propranolol or
Quinidine or
Radiopaque agents, water-soluble organic iodides, with intravascular administration    (concurrent use with these medications may impair blood pool images by decreasing the labeling efficiency of red blood cells {06})


Due to medical problems or conditions
Goiter, toxic diffuse or
Hyperthyroidism    (thyroid uptake may be increased {13})


Lupus erythematosus    (labeling of red blood cells may be decreased {13})


Transfusion-induced reaction    (labeling efficiency may be decreased because of red blood cell antibody formation {13})

With other diagnostic test results
Brain scan using sodium pertechnetate Tc 99m    (may give either false-positive or false-negative results when performed after a bone scan using technetium Tc 99m pyrophosphate that contains stannous ions; to avoid false results, brain scan should be performed prior to bone scan or with a brain imaging agent other than sodium pertechnetate Tc 99m {21})


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 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
Incidence less frequent or rare
    
Allergic reaction (skin rash, hives, or itching){01}{02}





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 bone and cardiac tissues and in labeled red blood cells

Retention of radioactivity allows visualization of skeletal or cardiac lesions, or visualization of blood pool

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 use should be considered





Breast-feeding—Not known if technetium Tc 99m pyrophosphate is 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
Special preparatory instructions may be given; patient should inquire in advance

For cardiac and skeletal imaging: Increasing intake of fluids and voiding frequently after injection and before test begins to minimize radiation dose to bladder; voiding again just prior to imaging for best test results

Precautions after having this test
For cardiac and skeletal imaging: Increasing intake of fluids and voiding frequently for 4 to 6 hours after test to minimize radiation dose to bladder


Side/adverse effects
Signs of potential side effects, especially allergic reaction


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. {19}

Manufacturer's package insert or other appropriate literature should be consulted for optimal times when imaging should be performed.

For cardiac and skeletal imaging
Unless cardiac status indicates otherwise, the patient should increase intake of fluids and void frequently following the administration of technetium Tc 99m pyrophosphate injection, and for 4 to 6 hours after the imaging procedures are completed, to minimize radiation dose to the bladder. {01}

Voiding is also recommended immediately prior to imaging procedures to reduce background interference that may result from accumulation of the agent in the bladder. {01}

For blood pool imaging (cardiac blood pool imaging and diagnosis of gastrointestinal bleeding)
Stannous pyrophosphate should be injected by direct venipuncture. Heparinized catheter systems are not recommended.

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. {23}


Parenteral Dosage Forms

TECHNETIUM Tc 99m PYROPHOSPHATE INJECTION USP

Usual adult and adolescent administered activity


For technetium Tc 99m pyrophosphate:
Skeletal imaging or

Cardiac imaging—Intravenous, 555 to 740 megabecquerels (15 to 20 millicuries), administered over a period of ten to twenty seconds.



For sodium pyrophosphate without Tc 99m label:
Blood pool imaging—Intravenous, 5 to 15.4 mg of stannous pyrophosphate (unlabeled) followed, fifteen to sixty minutes later, by the intravenous administration of 740 megabecquerels (20 millicuries) of sodium pertechnetate Tc 99m. {01}


Usual pediatric administered activity
Dosage must be individualized by physician.

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

Strength(s) usually available
U.S.—


12 mg of sodium pyrophosphate and 3.4 mg of stannous chloride (anhydrous) per 10-mL reaction vial (Rx) [TechneScan PYP]


40 mg sodium pyrophosphate, 0.4 mg stannous fluoride (minimum), and 0.9 mg total tin (maximum) as stannous fluoride, per 5-mL reaction vial (Rx) [MPI Pyrophosphate] [Phosphotec]

Canada—
Not commercially available.

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

Note: Before reconstitution, store between 2 and 8 °C (36 and 46 °F). {01}


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

To prepare sodium pyrophosphate injection (unlabeled), stannous pyrophosphate is reconstituted with sodium chloride injection. See manufacturer's package insert for complete instructions.

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

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.

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. MPI Pyrophosphate package insert (Medi Physics—US), Rev 10/88.
  1. DPPR report received at USP.
  1. Chilton HM, Witcotski RL. Nuclear pharmacy—An introduction to the clinical application of radiopharmaceuticals. Philadelphia: Lea & Febiger, 1986.
  1. Hladik WB, et al. Drug-induced changes in biodistribution—Seminars in Nuclear Medicine, April 1982: 194-6.
  1. Hladik WB, Saha GB, Study KT. Essentials of nuclear medicine science. Baltimore: Williams & Wilkins, 1987.
  1. Laven DL, Clanton JA, Hladik WB, et al. Pharmacologic alterations in the biorouting/performance of select radiopharmaceuticals used in cardiac imaging. Monograph presented at SNM Annual Meeting 06/90.
  1. Goldstein SA, Lindsay J, Chandeysson PL, et al. Usefulness of technetium pyrophosphate scintigraphy in demonstrating cardiac amyloidosis in persons aged 85 years and older. Am J Cardiol 1988; 63: 752.
  1. Lopez-Majano V, Sansi P, Colter R. Nuclear medicine in the diagnosis of cardiac contusion. Eur J Nucl Med 198; 11: 290-4.
  1. Leinonen H, et al. Negative myocardial technetium-99m pyrophosphate scintigraphy in amyloid heart disease associated with type AA systemic amyloidosis. Am J Cardiol 1984; 53: 380-1.
  1. Parrish M, Graham TP. Radionuclide angiography in children. J Pediatr 1984; 104(2): 165-71.
  1. Technetium Tc 99m (Pyro- and Trimeta-) Phosphates monograph in USP-DI, 1990.
  1. Norwich Eaton comment 8/87 in Etidronate (Systemic) monograph, USP-DI.
  1. Shaw SM. Drugs and diseases that may alter the biodistribution or pharmacokinetics of radiopharmaceuticals. Pharmacy Int'l 1985 Dec: 293-8.
  1. MPI Pyrophosphate package insert (Medi-Physics—US), Rev 11/90.
  1. TechneScan PYP package insert (Mallinckrodt—US), Rev 8/90.
  1. USP Radiopharmaceuticals Advisory Panel meeting on 01/88.
  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.
  1. USP Radiopharmaceuticals Panel meeting on 5/8/91.
  1. USP Radiopharmaceuticals Panel meeting on 08/04/92.
  1. Hommeyer SH, Varney DM, Eary JF. Skeletal nonvisualization in a bone scan secondary to intravenous etidronate therapy. J Nucl Med 1992; 33: 748-50.
  1. Osteoscan-HDP package insert (Mallinckrodt—US), Rev 6/89.
  1. Reviewers' responses to technetium Tc 99m medronate monograph revision of 2/17/93.
  1. Reviewers' responses to Ballot of 5/11/94.
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