Technetium Tc 99m Oxidronate (Systemic)


VA CLASSIFICATION
Primary: DX201

Commonly used brand name(s): Osteoscan-HDP.

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)—

Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

Accepted

Skeletal imaging, radionuclide—Technetium Tc 99m oxidronate is indicated as a skeletal imaging agent in adults and children to delineate areas of abnormal osteogenesis, such as those that occur with metastatic bone disease, Paget's disease, arthritic disease, osteomyelitis, and fractures. {01} {05} {06}


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

Mechanism of action/Effect:

Exact mechanism is not known. It is generally accepted that technetium Tc 99m oxidronate localizes on the surface of hydroxyapatite crystals 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 oxidronate is altered in areas of abnormal osteogenesis. {15}

Distribution:

Rapidly distributed in and cleared from blood after intravenous administration, with about half the dose normally accumulating in the skeleton within 3 to 4 hours after injection {02}. May also locate within infarcted myocardial cells or other regions of soft tissue necrosis or calcification. Minimal uptake by soft-tissue organs, except calcified cartilage, blood vessels, and kidneys. {13} {17} {18}

Time to radioactivity visualization

1 to 4 hours (optimal imaging). {05} {16}

Radiation dosimetry:
{10}

Estimated absorbed radiation dose*
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)
* For adults; intravenous injection of technetium Tc 99m–labeled phosphates and phosphonates. Data based on the International Commission on Radiological Protection (ICRP) Publication 53—Radiation dose to patients from radiopharmaceuticals. {08}

Elimination:
    Renal. {01}


Precautions to Consider

Carcinogenicity/Mutagenicity

Long-term animal studies to evaluate carcinogenic or mutagenic potential of technetium Tc 99m oxidronate have not been performed. {06}

Pregnancy/Reproduction

Pregnancy—
Tc 99m (as free pertechnetate) crosses the placenta. Studies with technetium Tc 99m oxidronate 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. {08}

Studies have not been done in animals.

FDA Pregnancy Category C. {01} {06}

Breast-feeding

Although it is not known whether technetium Tc 99m oxidronate 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. {07}

Pediatrics

Diagnostic studies performed to date using technetium Tc 99m oxidronate 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 oxidronate in pediatric patients. When this radiopharmaceutical is used in children, the diagnostic benefit should be judged to outweigh the potential risk of radiation. {08}


Geriatrics


Appropriate studies on the relationship of age to the effects of technetium Tc 99m oxidronate 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
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 oxidronate in the liver)


Diatrizoate sodium    (possible renal and hepatic uptake if diatrizoate sodium is administered intravenously immediately after technetium Tc 99m oxidronate)


Etidronate    (etidronate may interfere with bone uptake of technetium Tc 99m oxidronate; discontinuation of etidronate therapy before performance of a bone scan with technetium Tc 99m oxidronate is recommended for a 2-week period {04} {14})


Heparin calcium, subcutaneous or
Iron dextran, intramuscular or
Meperidine, intramuscular    (possible accumulation of technetium Tc 99m oxidronate at site[s] of injection of these medications)


Iron supplements or preparations    (iron overload may cause a decrease in bone uptake of technetium Tc 99m oxidronate {03})


Potassium phosphates or
Potassium and sodium phosphates or
Sodium phosphates    (saturation of bone binding sites by phosphorus ions in these medications may cause decreased bone uptake of technetium Tc 99m oxidronate)


Due to medical problems or conditions
Bone demineralization, glucocorticoid-induced    (long-term therapy with glucocorticoids may induce bone mineral depletion, thus causing decreased bone uptake of technetium Tc 99m oxidronate)


Gynecomastia, estrogen-induced    (possible localization of technetium Tc 99m oxidronate in breast)


Nephrotoxicity, drug-induced    (increased retention of technetium Tc 99m oxidronate in kidneys {19})


Obesity    (decreased visualization may result due to attenuation of photons coming from bone)


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


Renal function impairment    (decreased clearance of technetium Tc 99m oxidronate from blood and soft tissues may impair 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 oxidronate)

With results of other tests
Brain imaging    (brain scans using sodium pertechnetate Tc 99m may result in high blood background activity when performed after a bone scan using technetium Tc 99m oxidronate, which contains stannous ions; to avoid this potential diagnostic interference, brain scan may be performed prior to bone scan or with a brain imaging agent other than sodium pertechnetate Tc 99m [e.g., technetium Tc 99m pentetate] {06} {19})


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 (flushing or redness of skin){01}{06}



Those indicating need for medical attention if they continue or are bothersome
Incidence less frequent or rare
    
Nausea and vomiting{05}{06}





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

Retention of radioactivity in bone allows visualization of lesions

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 oxidronate 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

Increasing intake of fluids and voiding frequently after injection and before test begins in order to minimize radiation dose to bladder

Voiding again just prior to imaging for best test results

Precautions after having this test
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. {09}

The patient should increase intake of fluids and void frequently following the administration of technetium Tc 99m oxidronate injection, and for 4 to 6 hours after the imaging procedures are completed, to minimize radiation dose to the bladder. {01} {06}

Voiding is also recommended immediately prior to imaging procedures to reduce background interference that may result from accumulation of the agent in the bladder. {06}

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. {20}


Parenteral Dosage Forms

TECHNETIUM Tc 99m OXIDRONATE INJECTION USP

Usual adult and adolescent administered activity
Skeletal imaging
Intravenous, 370 to 740 megabecquerels (10 to 20 millicuries), administered slowly.


Usual adult prescribing limits
Up to 740 megabecquerels (20 millicuries). {05}

Usual pediatric administered activity
Skeletal imaging
Intravenous, 7.4 to 13 megabecquerels (0.20 to 0.35 millicurie) per kg of body weight, administered slowly. {05} {06}

Note: The recommended minimum total pediatric administered activity is 37 megabecquerels (1 millicurie); the maximum total pediatric administered activity is 740 megabecquerels (20 millicuries). {05} {06} {11}



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

Strength(s) usually available
U.S.—


2.0 mg oxidronate sodium and 0.16 mg stannous chloride, per vial (Rx) [Osteoscan-HDP]

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.

Note: Both prior to and following radiolabeling, this product may be stored at or below room temperature. {06}


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 8 hours after preparation. {05} {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.

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. Osteoscan-HDP package insert (Mallinckrodt—US), Rev 7/83.
  1. Chilton HM, Witcofski RL: Nuclear Pharmacy—An introduction to the clinical application of radiopharmaceuticals. Philadelphia: Lea & Febiger, 1986: 121.
  1. Hladik WB, Saha GB, Study KT. Essentials of nuclear medicine science. Baltimore: Williams & Wilkins, 1987: 193, 201, 202.
  1. Norwich Eaton comment as of 8/87 in Etidronate (Systemic).
  1. Osteoscan-HDP package insert (Mallinckrodt—US), Rev 6/89.
  1. Osteoscan-HDP package insert (Mallinckrodt—US), Rev 6/91.
  1. USP Radiopharmaceuticals Advisory Panel meeting on 01/88.
  1. USP Radiopharmaceuticals Advisory Panel meeting on 05/08/91.
  1. USP Radiopharmaceuticals Panel meeting on 08/04/92.
  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: 215.
  1. Pediatric dosages as recommended by USP Radiopharmaceuticals Advisory panelists, 08/92.
  1. Ganz WI, Serafini AN. The diagnostic role of nuclear medicine in the acquired immunodeficiency syndrome. J Nucl Med 1989; 30: 1935-45.
  1. Reviewers' comments as per monograph revision of 8/90.
  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. Holder LE. Clinical radionuclide bone imaging. Radiology 1990; 176: 607-14.
  1. Delaloye B, Delaloye-Bischof A, Koppenhagen K, et al. Clinical comparison of Tc 99m-HMDP and Tc 99m-MDP. A multicenter study. Eur J Nucl Med 1985; 11(5): 182-5.
  1. Fogelman I, Pearson DW, Bessent RG, et al. A comparison of skeletal uptakes of three diphosphonates by whole-body retention. J Nucl Med 1981; 22: 880-3.
  1. O'Connor MK, Brown ML, Hung JC, et al. The art of bone scintigraphy-technical aspects. J Nucl Med 1991; 32: 2332-41.
  1. Reviewers' comments as per technetium Tc 99m medronate monograph revision of 2/17/93.
  1. Reviewers' responses to Ballot of 5/11/94.
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