Document
DailyMed Label: CardioGen-82
Title
DailyMed Label: CardioGen-82
Date
2024
Document type
DailyMed Prescription
Name
CardioGen-82
Generic name
Rubidium Chloride RB-82
Manufacturer
Bracco Diagnostics Inc
Product information
NDC: 0270-0091
Product information
NDC: 0270-0091
Product information
NDC: 0270-0091
Product information
NDC: 0270-0091
Description
CardioGen-82 contains accelerator-produced Sr
82 adsorbed on stannic oxide in a lead-shielded column and provides
a means for obtaining sterile nonpyrogenic solutions of rubidium Rb
82 chloride injection. The chemical form of Rb 82 is 82 RbCl.
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 Sr 82 and not more than 0.2 microcurie of Sr 85 per millicurie
of rubidium Rb 82 chloride injection, and not more than 1 microgram
of tin per mL of eluate.
Rb 82 decays by positron emission and associated
gamma emission with a physical half-life of 75 seconds. 4 Table 5 shows the annihilation photons released
following positron emission which are useful for detection and imaging
studies.
The decay modes of Rb 82 are:
95.5% by positron emission, resulting in the production of annihilation
radiation, i.e., two 511 keV gamma rays; and 4.5% by electron capture,
resulting in the emission of “prompt” gamma rays of predominantly
776.5 keV. Both decay modes lead directly to the formation of stable
Kr-82. 4
TABLE
5 Principal Radiation Emission Data
Mean Percent
Mean Energy
Radiation
Per Disintegration
(keV)
Annihilation photons (2)
191.01
511 (each)
Gamma rays
13-15
776.5
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). Table 6 shows a range of values
for the relative attenuation of the radiation emitted by this radionuclide
that results from interposition of various thicknesses of lead. 5 For example, the use of a 7.0 centimeter thickness
of Pb will attenuate the radiation emitted by a factor of about 1,000.
TABLE
6 Radiation Attenuation by Lead Shielding
Shield Thickness
(Pb) cm
Attenuation
Factor
0.7
0.5
2.3
10 -1
4.7
10 -2
7.0
10 -3
9.3
10 -4
Sr 82 (half-life of 25 days (600 hrs.))
decays to Rb 82. To correct for physical decay of Sr 82, Table 7 shows
the fractions that remain at selected intervals after the time of
calibration.
*Calibration time
TABLE
7 Physical Decay Chart: Sr 82 half-life 25 days
Days
Fraction Remaining
Days
Fraction Remaining
Days
Fraction Remaining
0*
1.000
15
0.660
30
0.435
1
0.973
16
0.642
31
0.423
2
0.946
17
0.624
32
0.412
3
0.920
18
0.607
33
0.401
4
0.895
19
0.591
34
0.390
5
0.871
20
0.574
35
0.379
6
0.847
21
0.559
36
0.369
7
0.824
22
0.543
37
0.359
8
0.801
23
0.529
38
0.349
9
0.779
24
0.514
39
0.339
10
0.758
25
0.500
40
0.330
11
0.737
26
0.486
41
0.321
12
0.717
27
0.473
42
0.312
13
0.697
28
0.460
14
0.678
29
0.448
To correct for physical decay of Rb 82,
Table 1 shows the fraction of Rb 82 remaining in all 15 second intervals
up to 300 seconds after time of calibration [see Dosage and
Administration (2.6 , 2.7) ].
Indications
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.
CardioGen-82 is a closed system used to produce
rubidium Rb 82 chloride injection for intravenous use. Rubidium Rb
82 chloride injection is a radioactive diagnostic agent 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. (1)
Dosage
Use only additive free 0.9% Sodium Chloride Injection
USP to elute the generator . (2.5)
Use CardioGen-82 only with the CardioGen-82 Infusion System
Model 510 or Model 1700. (2.4)
The recommended adult (70 kg) single dose of rubidium Rb
82 chloride injection is 1,480 MBq (40 mCi), with a range of 1,110
MBq to 2,220 MBq (30 mCi to 60 mCi). Do not exceed a single dose of
2,220 MBq (60 mCi) per rest or stress component of a procedure. (2.2)
Administer via intravenous infusion at a rate of 50 mL/minute
(Model 510 and Model 1700), or at a rate of 20 mL/minute (Model
1700 only ). (2.2)
Use the lowest dose necessary to obtain adequate cardiac
visualization. Individualize the dose depending on multiple factors,
including patient weight, imaging equipment and acquisition type used
to perform the procedure. (2.2)
Start imaging acquisition 60 to 90 seconds after completion
of the infusion; if a longer circulation time is anticipated, wait
for 120 seconds. Image acquisition is typically 5 minutes long. (2.3)
To obtain both rest and stress images, wait 10 minutes after
completion of the rest image acquisition, then administer the pharmacologic
stress agent in accordance with its prescribing information. Then,
at a time interval after the administration of the pharmacologic stress
agent that is in accordance with its prescribing information, infuse
the second dose of rubidium Rb 82 chloride and complete the stress
image acquisition. (2.3)
Rubidium Rb 82 is a radioactive drug and should be handled
with appropriate safety measures to minimize radiation exposure during
administration [See Warnings and Precautions (5.5) ].
Use only additive-free 0.9% Sodium Chloride Injection
USP to elute the generator
[see Boxed
Warning , Contraindications (4) , and Warnings and Precautions (5.1) ] .
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.
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.
The recommended adult single dose of rubidium
Rb 82 chloride injection per rest or stress component of a PET myocardial
perfusion imaging (MPI) procedure is 1,480 MBq (40 mCi) with a range
of 1,110 MBq to 2,220 MBq (30 mCi to 60 mCi).
Do not exceed a single dose of 2,220 MBq (60 mCi).
Use the lowest dose necessary, consistent with the goal
of as low as reasonably achievable (ALARA), to obtain adequate cardiac
visualization. The choice of dosage and infusion rate should be made
at the discretion of the physician performing the Rb 82 PET myocardial
perfusion imaging scan, based on his/her consideration of multiple
factors, including patient body mass, and the imaging equipment and
acquisition methodology used to perform the procedure. For example,
3D image acquisition may require doses at the lower end of the recommended
range, compared to 2D imaging.
Administer the single dose at 50 mL/minute, or at
20 mL/minute (CardioGen-82 Infusion System Model 1700 only) , through a catheter inserted into a large peripheral vein; do not
to exceed a total infusion volume of 100 mL.
Instruct patients to void as soon as a study is completed
and as often as possible thereafter for at least one hour.
The maximum available activity (delivery limit) will decrease
as the generator ages [see Dosage and Administration (2.9) ].
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 to 90 seconds after completion of the infusion
of the rest dose, and acquire images for 5 minutes.
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 the administration of the pharmacologic stress agent,
administer the second dose of Rb 82 at the time interval according
to the prescribing information of the pharmacologic stress agent;
Start imaging 60 to 90 seconds after completion of the stress
Rb 82 chloride dose infusion, and acquire images for 5 minutes.
For Both
Rest and Stress Imaging:
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.
Acquisition may be started immediately post-injection if
dynamic imaging is needed.
Use CardioGen-82 only with the CardioGen-82 Infusion System
Model 510 or the CardioGen-82 Infusion System Model 1700, which are
specifically designed for use with the generator and capable of accurate
measurement and delivery of doses of rubidium Rb 82 chloride injection.
If using the CardioGen-82 Infusion System Model 510, refer
to the Eluate Testing Protocol in Section 2.6 [see Dosage
and Administration (2.6) ] .
If using the CardioGen-82 Infusion System Model 1700, refer
to the Eluate Testing Protocol in Section 2.7 [see Dosage
and Administration (2.7) ] .
Follow instructions in the CardioGen-82 Infusion System
Model 510 or Model 1700 Operator’s Manual for the set up and intravenous
infusion of rubidium Rb 82 chloride injection dose(s). 1,2
The generator, when used with either infusion system, provides
± 10% accuracy for rubidium Rb 82 chloride injection between doses
of 1,110 MBq to 2,220 MBq (30 mCi to 60 mCi).
Use only additive-free 0.9 % Sodium
Chloride Injection USP to elute the generator
[see Boxed Warning , Contraindications (4) , and Warnings and Precautions (5.1) ] .
Prepare the 0.9 % Sodium Chloride Injection
USP for use with the Saline Tag
Prepare the intravenous port in accordance with the DOSAGE
AND ADMINISTRATION section of the approved prescribing information
of the 0.9 % Sodium Chloride Injection USP.
The intravenous administration port of the sodium chloride
container must be penetrated only one time.
Strap the saline tag provided with the CardioGen-82 Infusion
System on the additive-free 0.9% Sodium Chloride Injection USP container
and install on the CardioGen-82 Infusion System.
Once the container port closure is penetrated, it should
remain installed on the CardioGen-82 Infusion System for its entire
period of use. A maximum of 12 hours from the initial port closure
penetration is permitted, after which the bag must be replaced for
the next patient.
Allow at least 10 minutes between elutions
for regeneration of Rb 82.
If the CardioGen-82 Infusion System Model
510 is used, discard the first 50 mL eluate each day the generator
is eluted, and employ proper safety precautions since the eluate contains
radioactivity. If the CardioGen-82 Infusion System Model 1700 is
used, the system will automatically discard the first 50 mL of eluate
each day the generator is eluted.
If the CardioGen-82 Infusion System Model
510 is used, 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. If the CardioGen-82 Infusion System
Model 1700 is used, the system software automatically records and
saves all eluate volumes (all flushing, Quality Control (QC) testing,
and patient infusions), representing the cumulative volume of eluate
each day the generator is eluted.
Use only additive-free 0.9% Sodium Chloride Injection
USP for all elutions
[see Boxed Warning , Contraindications (4) , and Warnings
and Precautions (5.1) ] .
Observe aseptic technique
throughout.
Follow all instructions in the CardioGen-82 Infusion System
Model 510 Operator’s Manual for performing all eluate testing as described.
Before administering
rubidium Rb 82 chloride injection to the first patient each day, perform
the following testing:
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 points.
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:
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.
Elute the generator with 50 mL of Sodium Chloride Injection
USP and discard the eluate (first elution).
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.).
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:
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.
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 in the display.
Calculate the ratio (R) of Sr 85/Sr 82 on the day (postcalibration)
of the measurement using the ratio of Sr 85/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] / [Sr 82] on calibration date X Ratio Factor on the day (post-calibration)
of measurement
Use a correction factor (F) of 0.478 to compensate for the
contribution of Sr 85 to the reading.
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 / [1 + (1.48)(0.478)] = 0.47
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 or Sr 82; 50 mCi of Rb 82 E.O.E. 0.47
μCi Sr 82 / 50 mCi Rb 82 = 0.0094 μCi/mCi Rb 82 (is above Alert Limit
of 0.002; additional daily eluate testing must be performed)
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).
*Elution time
TABLE
1 Physical Decay Chart: Rb 82 half-life 75 seconds
Seconds
Fraction Remaining
Seconds
Fraction Remaining
0*
1.000
165
0.218
15
0.871
180
0.190
30
0.758
195
0.165
45
0.660
210
0.144
60
0.574
225
0.125
75
0.500
240
0.109
90
0.435
255
0.095
105
0.379
270
0.083
120
0.330
285
0.072
135
0.287
300
0.063
150
0.250
Use Table 2 to calculate
the ratio (R) of Sr 85/Sr 82; step 7 (above).
*Day of calibration
TABLE
2 Sr 85/Sr 82 Ratio Chart (Sr 85 T ½ = 65 days, Sr 82 T ½ = 25 days)
Days
Ratio Factor
Days
Ratio Factor
Days
Ratio Factor
0*
1.00
15
1.29
30
1.67
1
1.02
16
1.31
31
1.70
2
1.03
17
1.34
32
1.73
3
1.05
18
1.36
33
1.76
4
1.07
19
1.38
34
1.79
5
1.09
20
1.41
35
1.82
6
1.11
21
1.43
36
1.85
7
1.13
22
1.46
37
1.88
8
1.15
23
1.48
38
1.91
9
1.17
24
1.51
39
1.95
10
1.19
25
1.53
40
1.98
11
1.21
26
1.56
41
2.01
12
1.23
27
1.58
42
2.05
13
1.25
28
1.61
14
1.27
29
1.64
Use only additive-free
0.9% Sodium Chloride Injection USP for all elutions
[see Boxed Warning , Contraindications (4) , and Warnings and Precautions (5.1) ] .
Observe aseptic
technique throughout.
Follow all instructions
in the CardioGen-82 Infusion System Model 1700 Operator’s Manual for
performing all elute testing as described.
Perform
Mandatory Eluate Testing to determine Rb 82, Sr 82, and Sr 85 levels:
Daily – Before administering rubidium
Rb 82 chloride injection to the first patient each day.
Repeat as indicated after an Alert Limit
has been detected.
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.
The CardioGen-82 Infusion System Model
1700 will automatically indicate when alert limits have been reached,
and will require that additional tests be performed, to facilitate
the prompt detection of excessive levels of Sr 82 and/or Sr 85 should
they occur.
These additional daily eluate tests will
be performed at intervals determined by the day’s elution volume,
and will be enforced by the System software. Specifically, the infusion
system will require the user to perform additional eluate testing
after each 750 mL of elution volume when any Alert Limit parameter
has been reached.
Infusion System Calibration : Before administering rubidium
Rb 82 chloride injection to the first patient:
After installation of a new generator and / or installation of a
new CardioGen-82 Accessory Package, Item # 001710, perform the Rubidium
Rb 82 Chloride Injection Dose Calibration (performed using an external
dose calibrator).
Set a dose calibrator for Rb 82 as recommended
by the manufacturer. Obtain the reading from the instrument in millicuries.
Following the prompts in the Graphical
User Interface (GUI) for the CardioGen-82 Infusion System Model 1700,
elute the generator with additive-free 0.9% Sodium Chloride Injection
USP at a rate of 50 mL/min and collect the eluate in the stoppered
vial specifically provided for use with the CardioGen-82 Infusion
System Model 1700 (alternative vials, glass or plastic are not suitable).
Note the exact time of end of elution (EOE).
Using the external dose calibrator, assay
the eluate at exactly 2:30, 3:45, or 5:00 minutes after EOE.
Following the prompts in the GUI for
the CardioGen-82 Infusion System Model 1700, enter the Rb 82 reading
from the dose calibrator and the time since EOE.
The infusion system software will automatically
calculate the Calibration Ratio.
If the ratio is within +/- 2% (0.98 to 1.02), the infusion
system will allow acceptance of the calibration factor that was used
for the elution.
If the ratio is not within +/- 2% (0.98 to 1.02), the system
requires another calibration elution (steps 1 through 4).
Repeat steps 1 through 4 for a flow rate
of 20 mL/min.
Perform
additional system calibration every 14 days.
Daily Quality Control : Eluate (Strontium Level) Testing
and Dose Constancy
Each day, before administering
rubidium Rb 82 chloride injection, perform the following test, including
Mandatory Eluate Testing:
Daily Quality
Control (performed on-board the CardioGen-82 Infusion
System Model 1700, using the gamma (Sr) detector):
Place the stoppered vial, which is specifically
provided for use with the CardioGen-82 Infusion System, Model 1700
(alternative vials, glass or plastic are not suitable) in the Sr detector
well on the CardioGen-82 Infusion System Model 1700 and, following
the prompts in the GUI for the infusion system, initiate the Daily
Quality Control workflow.
The infusion system will automatically
perform the Sr Detector Background Reading.
The infusion system will automatically
perform the Generator Column Wash.
Strontium Level Test and Dose Constancy:
The infusion system will elute the generator with 50 mL
of additive-free 0.9% Sodium Chloride Injection USP at a rate of 50
mL/min into the stoppered vial (which is specifically provided for
use with the CardioGen-82 Infusion System Model 1700).
The Sr detector measures the Rb 82 and strontium in the
50 mL elution.
The infusion system software will automatically calculate
the Sr 82 and Sr 85 levels on the day (post calibration) of the measurement
using the ratio of Sr 85/Sr 82 on the day of calibration provided
on the generator label, and using the full exponential decay calculation
for each, accounting for the generator’s age.
Using the Rb 82 and strontium measurements, the infusion
system software will automatically calculate µCi Sr 82/mCi Rb 82 and
µCi Sr 85/mCi Rb 82. The GUI will automatically indicate if the results
exceed Alert or Expiration Limits.
The infusion system software will automatically calculate
Dose Constancy.
Constancy Check of the Sr detector: The
infusion system GUI will prompt the user to perform the constancy
check of the Sr detector.
Place the external constancy source in the detector well
of the infusion system.
The infusion system software will automatically calculate
the constancy of the Sr detector versus the external constancy source
when instructed.
If using the CardioGen-82 Infusion System
Model 510, stop use of the CardioGen-82 generator once any one of
the following Expiration Limits is reached. If using the CardioGen-82
Infusion System Model 1700, the software will automatically indicate,
and will 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 maximum available
activity (delivery limit) will decrease as the generator ages. Certain
doses, including the maximum recommended dose [60 mCi ( 2,220 MBq)]
are not achievable for the entire shelf-life of the generator. Table
3 provides an estimate of the maximum available activity of Rubidium
Rb 82 (Delivery Limit) as a function of generator age.
1 Estimate
is based on a 100 mCi (3,700 MBq) Sr 82 generator at calibration.
2 Generator age at which delivery limit
is reached varies with generator activity at release. For example,
a 90 mCi (3,330 MBq) generator and a 150 mCi (5,550 MBq) generator
will reach a delivery limit <60 mCi at ≥ 14 days and ≥ 33 days,
respectively.
Table 3 Rubidium Rb 82 Dose Delivery Limit Based on Generator
Age 1
Generator Age (days) 2
Maximum Rubidium Dose (Delivery Limit)
0-17
60 mCi (2,220 MBq)
24
50 mCi (1,850 MBq)
32
40 mCi (1,480 MBq)
42
30 mCi (1,110 MBq)
The estimated absorbed radiation doses
for Rb 82, Sr 82, and Sr 85 from an intravenous injection of rubidium
Rb 82 chloride are shown in Table 4.
a Rb 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.
b Sr 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
c To 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 -13 Sv/Bq.
d Calculated from ICRP 66
e Calculated from ICRP 60
f Stress
phase only
Table 4 Adult Absorbed Radiation
Dose Coefficient
Organ a,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
Adrenals
7.56
10.6
5.03
Bone – Osteogenic cells
1.86
---
---
Bone Surface
----
107
9.81
Brain
0.60
8.29
2.96
Breast
0.82
7.03
1.72
Gall Bladder Wall
3.17
8.47
2.82
Heart Wall
16.5
8.18
2.67
Kidneys
20.04
9.18
2.50
Liver
4.20
8.10
2.50
Lower Large Intestine Wall
2.84
51.8
5.14
Lungs d
10.7
8.25
2.84
Muscles
1.29
8.14
2.66
Ovaries
1.41
10.2
4.29
Pancreas
8.85
9.10
3.46
Red Marrow
1.19
91.0
9.84
Skin
1.14
7.03
1.75
Small Intestine
4.76
9.62
4.03
Spleen
6.61
8.10
2.54
Stomach
8.14
7.84
2.26
Testes
0.82
7.25
1.70
Thymus
1.49
7.84
2.33
Thyroid
6.11
8.07
2.57
Upper Large Intestine
5.94
23.7
3.62
Urinary Bladder Wall
1.61
21.9
2.90
Uterus
3.72
9.14
3.32
Total Body
1.77
Not calculated
Not calculated
Effective Dose e
4.74 f
23.4
4.03
Dosage forms
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 3,330 MBq to 5,550 MBq (90 millicuries to 150
millicuries) Sr 82 at calibration time.
CardioGen-82 consists of strontium Sr 82 adsorbed
on a hydrous stannic oxide column with an activity of 3,330 MBq to
5,550 MBq (90 millicuries to 150 millicuries) Sr 82 at calibration
time. (3)
Contraindications
CardioGen-82
is contraindicated if a solution other than additive free 0.9% Sodium
Chloride Injection USP has been used to elute the generator at any
time. Immediately stop the patient infusion and permanently discontinue
the use of the affected CardioGen-82 generator whenever the incorrect
eluent is used [see Boxed Warning ,
Contraindications (4) , and Warnings
and Precautions (5.1) ]
CardioGen-82 is contraindicated if a solution
other than additive free 0.9 % Sodium Chloride Injection USP has been
used to elute the generator at any time. (4)
Warnings
Pharmacologic induction of cardiovascular stress: May cause
serious adverse reactions such as myocardial infarction, arrhythmia,
hypotension, broncho-constriction, and cerebrovascular events. Perform
testing only in setting where cardiac resuscitation equipment and
trained staff are readily available. (5.3)
Use only additive free
0.9% Sodium Chloride Injection USP to elute the generator. Apply
the provided saline tag to the additive free 0.9% Sodium Chloride
Injection USP container before use. Additives present in other solutions
(particularly calcium ions) expose patients to high levels of radiation
by causing the release of large amounts of Sr 82 and Sr 85 into the
eluate regardless of the generator’s age or prior use [Dosage
and Administration (2.1 , 2.5 , and 2.6 , 2.7) ] .
Immediately stop the patient infusion
and discontinue use of the affected CardioGen-82 generator if the
incorrect eluent is used and evaluate the patient’s radiation absorbed
dose and monitor for the effects of radiation to critical organs such
as bone marrow. When solutions containing calcium ions are
used to elute the generator, high levels of radioactivity are present
in any subsequent eluate, even with the use of additive free 0.9%
Sodium Chloride Injection USP. [see Boxed
Warning , Dosage and Administration (2.10) and Contraindications (4) ] .
Excess radiation exposure occurs
when the Sr 82 and Sr 85 levels in rubidium Rb 82 chloride injections
exceed the specified generator eluate limits.
Strictly adhere to the eluate testing protocol
to minimize radiation exposure to the patient. Stop using the rubidium
generator when the expiration limits are reached [see Dosage
and Administration (2.6 , 2.7) and (2.8) ] .
Pharmacologic
induction of cardiovascular stress may be associated with serious
adverse reactions such as myocardial infarction, arrhythmia, hypotension,
bronchoconstriction, and cerebrovascular events. Perform pharmacologic
stress testing in accordance with the pharmacologic stress agent’s
prescribing information and only in the setting where cardiac resuscitation
equipment and trained staff are readily available.
Patients with congestive heart
failure or the elderly may experience a transitory increase in circulatory
volume load.
Rubidium Rb 82 chloride injection, similar
to other radiopharmaceuticals, contributes to a patient’s overall
long-term cumulative radiation exposure. Long-term cumulative radiation
exposure is associated with an increased risk of cancer. Use the lowest
dose of rubidium Rb 82 chloride injection necessary for imaging and
ensure safe handling to protect the patient and health care worker [see Dosage and Administration (2.1) and (2.2) ]. Encourage
patients to void as soon as a study is completed and as often as possible
thereafter for a least one hour.
Adverse reactions
Use in_specific_populations
Lactation: Do not resume breastfeeding until at least one
hour after completion of Cardiogen-82 infusion. (8.2)
Risk Summary
There are
no data available on the use of rubidium Rb 82 chloride in pregnant
women. Animal reproductive studies have not been conducted with rubidium
Rb 82 chloride injection. However, all radiopharmaceuticals have the
potential to cause fetal harm depending on the fetal stage of development
and the magnitude of the radiation dose. If considering rubidium Rb
82 chloride injection administration to a pregnant woman, inform the
patient about the potential for adverse pregnancy outcomes based on
the radiation dose from rubidium Rb 82 and the gestational timing
of exposure.
The estimated
background risk of major birth defects and miscarriage for the indicated
population is unknown. In the U.S. general population, the estimated
background risk of major birth defects and miscarriage in clinically
recognized pregnancies is 2-4% and 15-20%, respectively.
Risk Summary
There is no information
regarding the presence of Rb 82 chloride in human milk, the effects
on the breastfed infant or the effects on milk production. Due to
the short half-life of rubidium Rb 82 (75 seconds), exposure of a
breastfed infant through breast milk can be minimized by temporary
discontinuation of breastfeeding [See Clinical Considerations ]. The developmental and health benefits
of breastfeeding should be considered along with the mother’s clinical
need for Rb 82 chloride injection, any potential adverse effects on
the breastfed child from Rb 82 or from the underlying maternal condition.
Clinical Considerations
Minimizing
Exposure
Exposure to Rb 82 chloride through breast
milk can be minimized if breastfeeding is discontinued when Rb 82
chloride injection is administered. Do not resume breastfeeding until
at least one hour after completion of rubidium Rb 82 chloride injection
infusion.
Rubidium
Rb 82 chloride injection safety and effectiveness in pediatric patients
have not been established.
In elderly
patients with a clinically important decrease in cardiac function,
lengthen the delay between infusion and image acquisition [see Dosage and Administration (2.3) ]. Observe for the possibility of fluid overload [see Warnings and Precautions (5.4) ].
Reductions in renal function are not anticipated
to alter clearance of rubidium Rb 82 chloride injection because Rb
82 decays to stable Kr-82 with a half-life of 75 seconds and Kr-82
is exhaled through the lungs.
Reductions in hepatic function are not anticipated
to alter clearance of rubidium Rb 82 chloride injection.
How supplied
CardioGen-82 ® (rubidium Rb 82 generator), used to produce rubidium
Rb 82 chloride injection, consists of Sr 82 adsorbed on a hydrous
stannic oxide column with an activity of 3,330 MBq to 5,550 MBq (90
millicuries to 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.
Use CardioGen-82 (rubidium Rb 82 Generator) only with an appropriate,
properly calibrated infusion system labeled for use with the generator.
Store the generator at 20° to 25°C (68° to 77°F) [See USP].
Receipt, transfer, possession, storage, disposal or use
of this product is subject to the radioactive material regulations
and licensing requirements of the U.S. Nuclear Regulatory Commission
(NRC), Agreement States or Licensing States as appropriate. Do not
dispose of the generator in regular refuse systems.
For questions about the disposal of the CardioGen-82 generator,
contact Bracco Diagnostics Inc. at 1-800-447-6883, option 3.
Clinical pharmacology
Rb 82 is analogous to potassium ion (K + ) in its biochemical behavior and is rapidly extracted by the myocardium
proportional to the blood flow. Rb + participates
in the sodium-potassium (Na + /K + ) ion exchange pumps that are present in cell membranes.
The intracellular uptake of Rb 82 requires maintenance of ionic gradient
across cell membranes. Rb 82 radioactivity is increased in viable
myocardium reflecting intracellular retention, while the tracer is
cleared rapidly from necrotic or infarcted tissue.
In
human studies, myocardial activity was noted within the first minute
after peripheral intravenous injection of Rb 82. When areas of infarction
or ischemia are present in the myocardium, they are visualized within
2-7 minutes after injection as photon-deficient, or “cold”, areas
on the myocardial scan. In patients with reduced cardiac function,
transit of the injected dose from the peripheral infusion site to
the myocardium may be delayed [see Dosage and Administration (2.3) ].
Blood flow brings Rb 82 to all areas of
the body during the first pass of circulation. Accordingly, visible
uptake is also observed in other highly vascularized organs, such
as the kidneys, liver, spleen and lungs.
With
a physical half-life of 75 seconds, Rb 82 is very rapidly converted
by radioactive decay into a trace amount of stable Kr-82 gas, which
is passively expired by the lungs.
Nonclinical toxicology
No long-term studies have been performed to evaluate
carcinogenic potential, mutagenicity potential, or to determine whether
rubidium Rb 82 chloride injection may affect fertility in males or
females.
Clinical studies
In a
descriptive, prospective, blinded image interpretation study 6 of adult patients with known or suspected coronary
artery disease, myocardial perfusion deficits in stress and rest PET
images obtained with ammonia N 13 (n = 111) or rubidium Rb 82 chloride
(n = 82) were compared to changes in stenosis flow reserve (SFR) as
determined by coronary angiography. PET perfusion defects at rest
and stress for seven cardiac regions (anterior, apical, anteroseptal,
posterolateral, anterolateral, posterolateral, and inferior walls)
were graded on a scale of 0 (normal) to 5 (severe). Values for stenosis
flow reserve, defined as flow at maximum coronary vasodilatation relative
to rest flow, ranged from 0 (total occlusion) to 5 (normal). With
increasing impairment of flow reserve, the subjective PET defect severity
increased. A PET defect score of 2 or higher was positively correlated
with flow reserve impairment (SFR<3).
A system review of published literature was conducted using pre-defined
inclusion/exclusion criteria which resulted in identification of 10
studies evaluating the use of Rb 82 PET myocardial perfusion imaging
(MPI) for the identification of coronary artery disease as defined
by catheter-based angiography. In these studies, the patient was the
unit of analysis and 50% stenosis was the threshold for clinically
significant coronary artery disease (CAD). Of these 10 studies, 9
studies were included in a meta-analysis for sensitivity (excluding
one study with 100% sensitivity) and 7 studies were included in a
meta-analysis of specificity (excluding 3 studies with 100% specificity).
A random effects model yielded overall estimates of sensitivity and
specificity of 92% (95% CI: 89% to 95%) and 81% (95% CI: 76% to 86%),
respectively. The use of meta-analysis in establishing performance
characteristics is limited, particularly by the possibility of publication
bias (positive results being more likely to be published than negative
results) which is difficult to detect especially when based on a limited
number of small studies.
Package label
CardioGen-82 NDC: 0270–0091–01 Rubidium Rb 82 Generator
cardiogen-82-container-label
1 organization
1 product
Product
CardioGen-82Organization
Bracco Diagnostics Inc