cardiogen-82 (Rubidium Rb-82) injection, solution
[Bracco Diagnostics Inc.]
For Elution of Rubidium Chloride
Rb 82 Injection
Cardiogen-82® (Rubidium Rb 82 Generator) contains accelerator produced strontium Sr 82 adsorbed on stannic oxide in a lead-shielded column and provides a means for obtaining sterile nonpyrogenic solutions of rubidium chloride Rb 82 injection. The chemical form of rubidium 82 is 82RbCl.
The amount (millicuries) of Rb-82 obtained in each elution will depend on the potency of the generator.
When eluted at a rate of 50 mL/minute, each generator eluate at the end of elution should not contain more than 0.02 microcurie of strontium Sr 82 and not more than 0.2 microcurie of strontium Sr 85 per millicurie of rubidium chloride Rb 82 injection, and not more than 1 microgram of tin per mL of eluate.
Rubidium Rb 82 decays by positron emission and associated gamma emission with a physical half-life of 75 seconds.1 The annihilation photons released following positron emission which are useful for detection and imaging studies are shown in Table 1.
|Principal Radiation Emission Data|
|photons (2)||191.01||511 (each)|
The specific gamma ray constant for Rb-82 is 6.1 R/hour-millicurie at 1 centimeter. The first half-value layer is 0.7 centimeter of lead (Pb). A range of values for the relative attenuation of the radiation emitted by this radionuclide that results from interposition of various thicknesses of Pb is shown in Table 2. For example, the use of a 7.0 centimeter thickness of Pb will attenuate the radiation emitted by a factor of about 1,000.
|Radiation Attenuation by Lead Shielding|
Strontium Sr 82 decays to rubidium Rb 82 with a strontium Sr 82 half-life of 25 days (600 hrs). The Sr-82 is produced in an accelerator by proton spallation of molybdenum, Mo (p, spall) Sr-82 or by the reaction Rb-85 (p, 4n) Sr-82. The Sr-82 produced has no carrier added. To correct for physical decay of strontium Sr 82, the fractions that remain at selected intervals after the time of calibration are shown in Table 3.
|Physical Decay Chart: Sr-82 half-Iife 25 days|
To correct for physical decay of rubidium Rb 82, the fraction of rubidium chloride Rb 82 injection remaining in all 15 second intervals up to 300 seconds after time of calibration are shown in Table 4.
|Physical Decay Chart: Rb-82 half-life 75 seconds|
Following intravenous administration, rubidium Rb 82 rapidly clears the blood and is extracted by myocardial tissue in a manner analogous to potassium. In human studies, myocardial activity was noted within the first minute after injection. When areas of myocardial infarction are detected with rubidium chloride Rb 82 injection, they are visualized within two to seven minutes after injection as photon-deficient or "cold areas" on the myocardial scan. Uptake is also observed in kidney, liver, spleen, and lung.
Rubidium chloride Rb 82 injection is a myocardial perfusion agent that is useful in distinguishing normal from abnormal myocardium in patients with suspected myocardial infarction.
Cardiogen-82 (Rubidium Rb 82 Generator) must be used with an infusion system specifically labeled for use with the generator and capable of accurate measurement and delivery of doses of rubidium chloride Rb 82 injection not to exceed a single dose of 2220 MBq (60 mCi) and a cumulative dose of 4440 MBq (120 mCi) at a rate of 50 mL/min with a maximum volume per infusion of 100 mL and a cumulative volume not to exceed 200 mL. These performance characteristics reflect the conditions of use under which the drug development clinical trials were conducted.
Adequate data from clinical trials to determine precise localization of myocardial infarction or identification of stress-induced ischemia have not been collected.
Positron emission tomographic (PET) instrumentation is recommended for use with rubidium chloride Rb 82 injection.
Caution should be used during infusion as patients with congestive heart failure may experience a transitory increase in circulatory volume load. These patients should be observed for several hours following the Rb-82 procedure to detect delayed hemodynamic disturbances.
Data are not available concerning the effect of marked alterations in blood glucose, insulin, or pH (such as is found in diabetes mellitus) on the quality of rubidium chloride Rb 82 scans. Attention is directed to the fact that rubidium is physiologically similar to potassium, and since the transport of potassium is affected by these factors, the possibility exists that rubidium may likewise be affected.
Rubidium chloride Rb 82 injection must be administered only with an appropriate infusion system capable of meeting the performance characteristics previously described. (See INDICATIONS AND USAGE). The drug should be used only by those practitioners with a thorough understanding of the use and performance of the infusion system.
Repeat doses of Rubidium chloride Rb 82 injection may lead to an accumulation of the longer lived radioactive contaminants strontium Sr 82 and strontium Sr 85.
Since eluate obtained from the generator is intended for intravenous administration, aseptic techniques must be strictly observed in all handling. Only additive free Sodium Chloride Injection USP should be used to elute the generator. Do not administer eluate from the generator if there is any evidence of foreign matter.
As in the use of any radioactive material, care should be taken to minimize radiation exposure to the patient consistent with proper patient management and to insure minimum radiation exposure to occupational workers.
Radiopharmaceuticals should be used only by physicians who are qualified by training and experience in the safe use and handling of radionuclides and whose experience and training have been approved by the appropriate government agency authorized to license the use of radionuclides.
No long-term studies have been performed to evaluate carcinogenic potential, mutagenicity potential, or to determine whether rubidium Rb 82 may affect fertility in males or females.
Animal reproductive studies have not been conducted with rubidium Rb 82. It is also not known whether rubidium Rb 82 can cause fetal harm when administered to a pregnant woman or can affect reproductive capacity. Rubidium Rb 82 should be given to pregnant women only if the expected benefits to be gained clearly outweigh the potential hazards.
Ideally, examinations using radiopharmaceuticals, especially those examinations which are elective in nature, in women of childbearing capability should be performed during the first few (approximately 10) days following the onset of menses.
It is not known whether rubidium Rb 82 is excreted in human milk. Due to the short half-life of rubidium Rb 82 (75 sec) it is unlikely that the drug would be excreted in human milk during lactation. However, because many drugs are excreted in human milk, caution should be exercised when rubidium Rb 82 is administered to nursing women.
Safety and effectiveness in children have not been established.
No adverse reactions specifically attributable to rubidium Rb 82 have been reported during controlled clinical trials.
As with all radiopharmaceuticals, only the lowest dose of rubidium Rb 82 necessary to obtain adequate visualization should be used. A lower dose provides less patient radiation and is consistent with the achievement of ALARA. Most procedures do not require use of the maximum dose of rubidium Rb 82; the dose to be used should be carefully individualized and factors such as:
should be considered.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administrationwhenever solution and container permit.
An appropriate infusion system labeled for use with Cardiogen-82 (Rubidium Rb 82 Generator) is required. Please see DIRECTIONS FOR ELUTING RUBIDIUM CHLORIDE Rb 82 INJECTION below for additional information. (See also INDICATIONS AND USAGE).
Rubidium Rb 82 assay and strontium Sr 82 breakthrough should be determined each day the generator is used (See directions below).
Rubidium chloride Rb 82 injection obtained from Cardiogen-82 (Rubidium Rb 82 Generator) is intended only for intravenous administration utilizing an appropriate infusion system that is labeled for use with the generator. The usual adult (70 kg) dose (single injection) is 1480 MBq (40 mCi) with a range of 1110-2220 MBq (30-60 mCi). The dose must be administered at a rate of 50 mL/minute not to exceed a cumulative volume of 200 mL. (See also WARNINGS).
A single dose of 2220 MBq (60 mCi) should not be exceeded. The radiation dosimetry for a 2220 MBq (60 mCi) dose is presented in Table 5. No more than 4440 MBq (120 mCi) should be administered in a multiple injection series.
Exceeding the recommended dosing limits should only be done after due consideration of: (a) the benefits to be obtained by the patient vs. the risks associated with additional radiation; (b) previous (or contemplated) procedures involving radiation which this patient has undergone or might undergo; and (c) the achievement of ALARA. Further consideration should be given to the effect of total volume of injectate, which increases with the number of injections, as discussed under WARNINGS.
The estimated absorbed radiation doses to an average adult patient (70 kg) from an intravenous injection of a recommended dose of 2220 MBq (60 mCi) of rubidium Rb 82 are shown in Table 5.
|Adult Absorbed Radiation Doses1|
|Organ||mGy/2220 MBq||rads/60 mCi|
|1Calculated by the Internal Dosimetry Center at Oak Ridge Associated Universities|
|Upper Large Intestine||1.91||0.19|
|Lower Large Intestine||1.91||0.19|
Based on data collected by Ryan et al. in two human subjects (J Nuc Med 25(5): P94) and on rat data of Kearfott (J Nuc Med 23(12):1128-1132. Contaminant levels of Sr-82 and Sr-85 assumed to be 10-7 and 2.5 X 10-7 relative to Rb-82.
For strontium, assumed distribution and retention:
Bone 50% tb = ∞ (uniformity distributed throughout
Testes 0.5% tb = 1.5 day
Remainder 49.5% tb = 1.5 day
Cardiogen-82® (Rubidium Rb 82 Generator) is supplied in the form of strontium Sr 82 adsorbed on a hydrous stannic oxide column with an activity of 90-150 millicuries Sr-82 at calibration time. The generator is encased in a lead shield surrounded by a labeled plastic container. Complete assay data for each generator are provided on the container label. Directions for determining the activity of rubidium Rb 82 eluted from the generator are provided in this monograph. Cardiogen-82 (Rubidium Rb 82 Generator) is intended for use only with an appropriate, properly calibrated infusion system labeled for use with the generator.
Receipt, transfer, handling, possession or use of
this product is subject to the radioactive material
regulations and licensing requirements of the U.S.
Nuclear Regulatory Commission, Agreement
States or Licensing States as appropriate.
Hospital personnel should monitor the amount of radioactivity present at the generator prior to its disposal. The generator should not be disposed of in regular refuse systems. Storage and/or disposal of the generator should be in accordance with the conditions of NRC radioactive materials license pursuant to 10 CFR, Part 20, or equivalent conditions pursuant to Agreement State Regulation.
The generator should be stored at 20-25°C (68-77°C) [See USP].
The expiration date is provided on the generator container label. Due to the short half-life of Rb-82, virtually all the radioactivity in the eluate decays within 15 minutes from the end of elution.
An appropriate infusion system labeled for use with Cardiogen-82 (Rubidium Rb 82 Generator) is required. The applicable operator's manual should be consulted for detailed directions on generator hookup, elution, and patient administration. Prior to use with patients, a thorough understanding of the use and performance of the system should be established.
The Cardiogen-82 (Rubidium Rb 82 Generator) package insert and the Rb-82 infusion system operator's manual should be read before beginning elution.
Additional information concerning eluting the Cardiogen-82 generator follows:
The rubidium chloride Rb 82 assay and strontium Sr 82 and strontium Sr 85 breakthrough are determined using an ionization chamber-type dose calibrator. Procedure 1 through 11 below must be performed daily prior to the use of rubidium chloride Rb 82 injection.
The assay of rubidium chloride Rb 82 injection is determined as follows:
To measure the Sr-82 breakthrough in the eluate, proceed as follows:
R = ———— on calibration date x ratio factor on the date
[Sr-82] of measurement
dose calibration reading (μCi)
Sr-82 (μCi) = ————————————————
[1 + (R) (F)]
Example: dose calibrator reading (μCi) = 0.80
Sr-85/Sr-82 ratio (R) = (1.48)
Correction factor (F) = 0.478
Sr-82 (μCi) = —————————
[1 + (1.48)(0.478)]
Sr-82 (μCi) = 0.47
0.47 μCi of Sr-82
50 mCi of Rb-82 E.O.E.
0.47 μCi Sr-82 = 0.0094 = 9.4 X 10-3μCi/mCi Rb-82
50 mCi Rb-82
The Sr-82 content must not be more than 2 x 10-2μCi/mCi of Rb-82 at E.O.E.
9.4 x 10-3 x 1.48 = 1.4 x 10-2μCi Sr-85/mCi Rb-82
The Sr-85 content must not be more than 0.2 μCi/mCi of Rb-82 at E.O.E.
|Sr-85/Sr-82 Ratio Chart|
|Days||Ratio Factor||Days||Ratio Factor|
|*Day of calibration|
Bracco Diagnostics Inc.
Princeton, NJ 08543
by Medi-Physics, Inc.,
South Plainfield, NJ 07080
Printed in USA
Revised May 2000
|CardioGen-82 (Rubidium Rb-82)|
Data are from FDA and U.S. National Library of Medicine.