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
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 Â 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
- 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
Directions for Eluting Rubidium Rb 82 Chloride Injection
- Allow at least 10 minutes between elutions for regeneration
- 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
- 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
- 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
- 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:
|| 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
|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) =
|| = 0.47
|[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
TABLE 1 : Physical Decay Chart: Rb-82 half-life 75
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)
|*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
Table 3 : Adult Absorbed Radiation Dose Coefficient
||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
| Bone Surface
|Gall Bladder Wall
|Lower Large Intestine Wall
|Upper Large Intestine
|Urinary Bladder Wall
|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
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
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: 2/2012