"ATLANTA, GA â€” The Centers for Disease Control and Prevention (CDC) has issued a warning for healthcare providers and patients to be aware of a potential risk of infection from certain devices used during many open-heart surgeries.
CardioGen-82 is a closed system used to produce rubidium Rb 82 chloride injection for intravenous administration. Rubidium Rb 82 chloride injection is indicated for Positron Emission Tomography (PET) imaging of the myocardium under rest or pharmacologic stress conditions to evaluate regional myocardial perfusion in adult patients with suspected or existing coronary artery disease.
DOSAGE AND ADMINISTRATION
Use CardioGen-82 only with an infusion system specifically designed for use with the generator and capable of accurate measurement and delivery of doses of rubidium Rb 82 chloride injection. Follow instructions in the Infusion System User's Guide for the set up and intravenous infusion of rubidium Rb 82 chloride injection dose(s).
Rubidium Rb 82 Chloride Injection Dosage
The recommended adult single dose of rubidium Rb 82 chloride injection is 1480 MBq (40 mCi) with a range of 1110-2220 MBq (30-60 mCi).
- Do not exceed a single dose of 2220 MBq (60 mCi).
- Use the lowest dose necessary to obtain adequate cardiac visualization consistent with the dosing goal of as low as reasonably achievable (ALARA).
- Individualize the dose by considering factors such as body size, and the imaging equipment and technique.
- Administer the single dose at 50 mL/minute through a catheter inserted into a large peripheral vein; do not to exceed a total infusion volume of 100 mL.
Administer two separate single doses to complete rest and stress myocardial perfusion imaging as follows:
For rest imaging:
- Administer a single (“rest”) rubidium Rb-82 chloride dose;
- Start imaging 60-90 seconds after completion of the infusion of the rest dose and acquire images for 5 minutes; if a longer circulation time is anticipated (e.g., in a patient with severe left ventricular dysfunction), start imaging 120 seconds after the rest dose.
For stress imaging:
- Begin the study 10 minutes after completion of the resting dose infusion, to allow for sufficient Rb-82 decay;
- Administer a pharmacologic stress agent in accordance with its prescribing information;
- After an interval of 3 minutes, infuse a single (“stress”) rubidium Rb-82 chloride dose;
- Start imaging 60-90 seconds after completion of the stress Rb-82 chloride dose infusion and acquire images for 5 minutes; if a longer circulation time is anticipated start imaging 120 sec after the stress dose.
- Limit the use of radiopharmaceuticals to 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.
- Wear waterproof gloves and effective shielding when handling rubidium Rb-82 chloride injection and the infusion system.
- Observe aseptic techniques in all drug handling.
- Use only additive-free Sodium Chloride Injection USP to elute the generator.
- Visually inspect the drug for particulate matter and discoloration prior to administration whenever solution and container permit. Do not administer eluate from the generator if there is any evidence of foreign matter.
Directions for Eluting Rubidium Rb 82 Chloride Injection
- Allow at least 10 minutes between elutions for regeneration of Rb-82.
- Elute with additive-free Sodium Chloride Injection USP only. Additives (particularly calcium ions, to which strontium ions are chemically analogous), may cause the release of substantial amounts of Sr-82 and/or Sr-85 into the eluate regardless of the age or prior use of the generator.
- Discard the first 50 mL eluate each day the generator is first eluted. Employ proper safety precautions since the eluate contains radioactivity.
- Maintain an on-going record of all eluate volumes (washing, testing, dosing volumes), including a summary of the cumulative volume of eluate from the generator.
Eluate Testing Protocol
Use additive-free sodium chloride injection USP for all elutions. Apply aseptic technique throughout.
Before administering rubidium Rb 82 chloride injection to the first patient each day, perform the following test:
Strontium Alert Limits and Mandatory Eluate Testing:
- Use an ionization chamber-type dose calibrator for eluate testing.
- Daily, before administering rubidium Rb 82 chloride injection to any patient, perform an eluate testing to determine Rb-82, Sr-82, and Sr-85 levels
- Perform additional daily eluate tests after detecting any of
the following Alert Limits:
- 14 L total elution volume has passed through the generator column, or
- Sr-82 level reaches 0.002 μCi per mCi Rb-82, or
- Sr-85 level reaches 0.02 μCi per mCi Rb-82.
Perform the additional daily eluate tests at time points determined by the day's elution volume; tests are performed every 750 mL.
- For example, if an Alert Limit were reached and the clinical site eluted less than 750 mL from the generator during the day, then no additional eluate tests would have been performed that day.
- If the same clinical site the next day eluted 1,500 mL from the generator, then the site would have performed three tests that day: 1) the required daily test that precedes any patient dosing, 2) a test at the 750 mL elution point, and 3) a test at the 1,500 mL elution point.
- If a generator's Alert Limit is reached, the clinical site performs the additional daily tests (at intervals of 750 mL) each subsequent day the generator is used. The additional tests are necessary to promptly detect excessive Sr-82 and/or Sr-85 in eluates.
Rubidium Eluate Level Testing
1. Set a dose calibrator for Rb-82 as recommended by the manufacturer or use the Co-60 setting and divide the reading obtained by 0.548. Obtain the reading from the instrument in millicuries.
2. Elute the generator with 50 mL of Sodium Chloride Injection USP and discard the eluate (first elution).
3. Allow at least 10 minutes for the regeneration of Rb-82, then elute the generator with 50 mL of Sodium Chloride Injection USP at a rate of 50 mL/min and collect the eluate in a stoppered glass vial (plastic containers are not suitable). Note the exact time of end of elution (E.O.E.).
4. Using the dose calibrator, determine the activity of Rb-82 and note the time of the reading. Correct the reading for decay to the E.O.E. using the appropriate decay factor for Rb-82 (see Table 1). Note: If the reading is taken 2 ½ minutes after end of elution, multiply the dose calibrator reading by 4 to correct for decay.
Strontium Eluate Level Testing
5. Using the sample obtained for the Rb-82 activity determination, allow the sample to stand for at least one hour to allow for the complete decay of Rb-82.
6. Measure the activity of the sample in a dose calibrator at the setting recommended by the manufacturer for Rb-82 and/or Sr-82. As an alternative, use the Co-60 setting and the reading obtained divided by 0.548. Set the instrument to read in microcuries and record the reading in the display.
7. Calculate the ratio (R) of Sr-85/Sr-82 on the day (postcalibration) of the measurement using the ratio of Sr85/Sr-82 on the day of calibration provided on the generator label and the Sr-85/Sr-82 Ratio Factor from Table 2. Determine R using the following equation:
|R =||[Sr-85]||on calibration date X Ratio Factor on the day (post-calibration) of measurement|
8. Use a correction factor (F) of 0.478 to compensate for the contribution of Sr-85 to the reading.
9. Calculate the amount of Sr-82 in the sample using the following equation:
|Sr-82 (μCi) =||dose calibration reading (μCi)|
|[1 + (R) (F)]|
Example: dose calibrator reading (μCi) = 0.8; Sr85/Sr82 ratio (R) =1.48; correction factor (F) = 0.478.
|Sr-82 (μCi) =||0.8||= 0.47|
|[1 + (1.48)(0.478)]|
10. Determine if Sr-82 in the eluate exceeds an Alert or Expiration Limit by dividing the μCi of Sr-82 by the mCi of Rb-82 at End of Elution (see below for further instructions based on the Sr-82 level)
Example: 0.47 μCi of Sr-82; 50 mCi of Rb-82 E.O.E.
|0.47 μCi Sr-82||= 0.0094 μCi/mCi Rb-82 (is above Alert Limit of 0.002; additional daily eluate testing must be performed|
|50 mCi Rb-82|
11. Determine if Sr-85 in the eluate exceeds an Alert or Expiration Limit by multiplying the result obtained in step 10 by (R) as calculated in step 7 (above).
Example: 0.0094 x 1.48 = 0.014 μCi Sr-85/mCi Rb-82 (test result is below Alert and Expiration Limits)
Use Table 1 to calculate the decay factor for Rb-82; step 4 (above).
TABLE 1 : Physical Decay Chart: Rb-82 half-life 75
|Seconds||Fraction Remaining||Seconds||Fraction Remaining|
Use Table 2 to calculate the ratio (R) of Sr-85/Sr-82; step 7 (above).
TABLE 2 : Sr-85/Sr-82
Ratio Chart (Sr-85 T ½= 65 days, Sr-82½= 25 days)
|Days||Ratio Factor||Days||Ratio Factor||Days||Ratio Factor|
|*Day of calibration|
Stop use of the CardioGen-82 generator once any one of the following Expiration Limits is reached.
- A total elution volume of 17 L has passed through the generator column, or
- 42 days post calibration date, or
- An eluate Sr-82 level of 0.01 μCi /mCi Rb-82, or
- An eluate Sr-85 level of 0.1 μCi /mCi Rb-82.
The estimated absorbed radiation doses for Rb-82, Sr-82, and Sr-85 from an intravenous injection rubidium Rb- 82 chloride are shown in Table 3.
Table 3 : Adult Absorbed Radiation Dose Coefficient
|Organa,b||Rb-82 (Average for Rest and Stress) mrem/mCi (μSv/3.7 MBq)c||Sr-82 mrem /μCi (μSv/3.7kBq)c||Sr-85 mrem/μCi (μSv/3.7kBq)c|
|Bone – Osteogenic cells||1.86||---||---|
|Gall Bladder Wall||3.17||8.47||2.82|
|Lower Large Intestine Wall||2.84||51.8||5.14|
|Upper Large Intestine||5.94||23.7||3.62|
|Urinary Bladder Wall||1.61||21.9||2.90|
|Total Body||1.77||Not Calculated||Not Calculated|
|Effective Dosee||4.74 f||23.4||4.03|
|aRb-82 doses are averages of rest and stress dosimetry data
(see Senthamizhchelvan et al.1,2). To calculate organ doses (mrem)
from Rb-82, multiply the dose coefficient for each organ by the administered
activity in mCi.
bSr-82 and Sr-85 doses are calculated using software package DCAL and ICRP dose coefficients. To calculate organ doses (mrem) attributable to Sr-82, and Sr-85, multiply the dose coefficients by the calculated amounts of strontium in μCi.3
cTo convert to SI units, insert the dose coefficient into the formula in parentheses, e.g. for adrenals 7.56 mrem/mCi = 7.56 μSv/37 MBq = 2.04 x 10-13Sv/Bq .
dCalculated from ICRP 66
eCalculated from ICRP 60
fStress phase only
Dosage Forms And Strengths
CardioGen-82 is a closed system used to produce rubidium Rb 82 chloride injection for intravenous use. CardioGen-82 consists of strontium Sr-82 adsorbed on a hydrous stannic oxide column with an activity of 90-150 millicuries Sr-82 at calibration time.
Storage And Handling
CardioGen-82® (rubidium Rb 82 generator) consists of Sr-82 adsorbed on a hydrous stannic oxide column with an activity of 90-150 millicuries Sr-82 at calibration time. A lead shield surrounded by a labeled plastic container encases the generator. The container label provides complete assay data for each generator. Directions for determining the activity of Rb-82 eluted from the generator are described above [see DOSAGE AND ADMINISTRATION]. Use CardioGen-82 (rubidium Rb 82 Generator) 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.
Licensee personnel should monitor the amount of radioactivity present within the generator prior to its disposal. Do not dispose of the generator in regular refuse systems. Store and/or dispose of the generator in accordance with the conditions of NRC radioactive materials license pursuant to 10 CFR, Part 20, or equivalent conditions pursuant to Agreement State Regulation. For questions about the disposal of the CardioGen-82 generator, contact Bracco Diagnostics Inc. at 1-800-447-6883, option 3.
Store the generator at 20-25°C (68-77°F) [See USP].
Manufactured for Bracco Diagnostics Inc. Princeton, NJ 08543 by Medi-Physics, Inc., South Plainfield, NJ 07080. Revised: 2/2012This monograph has been modified to include the generic and brand name in many instances.
Last reviewed on RxList: 2/15/2012
Additional Cardiogen-82 Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Get the latest treatment options.