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DOSAGE AND ADMINISTRATION

The recommended intravenous dose range for the average (70 kg) adult patient is 37 to 148 MBq (1 to 4 mCi) of Technetium Tc 99m Albumin Aggregated Injection after reconstitution with oxidant-free Sodium Pertechnetate Tc 99m Injection. The suggested range of particle numbers for a single injection is 200,000to 700,000 with the recommended number being approximately 350,000. Depending on the activity added and volume of the final reconstituted product, the volume of the dose may vary from 0.2 to1.4 mL.

In paediatric patients, the suggested intravenous dose to be employed for perfusion lung imaging is in the range of 0.925 MBq to 1.85 MBq per kilogram (25 to 50 µCi/kg) of body weight; a usual dose is 1.11 MBq per kilogram (30 µ Ci/kg), except in newborns, in whom the administered dose should be 7.4 MBq to 18.5 MBq (200 to 500 µ Ci). Not less than the minimum dose of 7.4 MBq (200 µ Ci) should be employed for this procedure. The number of particles will vary with age and weight of the paediatric patient as indicated in Table 5.

Table 5

Paediatric Radiation Dose from Tc 99m MAA
For Lung Imaging*
Age                        Newborn             1 year             5 years            10 years            15 years 
Weight (kg)                     3.5                12.1               20.3                33.5             55.0 
Maximum recommended      MBq      mCi       MBq           mCi   MBq          mCi   MBq           mCi   MBq        mCi dose in megabecquerels and millicuries          18.5         0.5   22.2          0.6    37          1.0   62.9          1.7   103.6      2.8 Range of particles        10,000 to          50,000 to           200,000 to         200,000 to          200,000 to administered               50,000             150,000             300,000            300,000             700,000 Absorbed radiation dose in milligray              mGy     rads          mGy     rads       mGy         rads       mGy        rads       mGy     rads and rads for the maximum dose
ORGAN
Total body                     0.60         0.06      0.30     0.03      0.31        0.031         0.48    0.048      0.41    0.041 Lungs                          19.00         1.9      6.60     0.66      5.80         0.58         8.70     0.87      7.70     0.77 Liver                          1.40         0.14      0.60     0.06      0.62        0.062         1.80     0.18      1.20     0.12 Bladder wall                   2.10        0.21(1)    1.50    0.15(1)    3.10        0.31(2)       3.90    0.39(2)    4.10     0.41 Ovaries                        0.38        0.038      0.20     0.02      0.19        0.019         0.44    0.044      0.41    0.041 Testes                         0.31        0.031      0.13    0.013      0.19        0.019         0.20     0.02      0.36    0.036 (1) 2.0 hour voiding interval
(2) 4.8 hour voiding interval

*Assumptions:
1. Used biologic data from Kaul et al., Berlin, 1973. (3)
2. For the newborn, 1-year old, and 5-year old, the “S” values calculated from the preliminary phantoms of ORNL were used. The 10-year old, 15-year old and adult “S” values were taken from Henrichs et al., Berlin, 1980. (4)

The number of particles available per millicurie dose of technetium Tc 99m will vary depending on the physical decay of the technetium that has occurred. The number of particles available in any dose and volume to be administered may be calculated by means of the following formulas: 

Va =              D            and             P =         Va             x              N C x Fr                                      VTc

Where:

Va = Volume to be administered in mL
D      = Desired dose to be administered in MBq (mCi)

C      = Concentration at calibration time of the sodium pertechnetate solution to be added to the reaction vial in MBq/mL (mCi/mL)

Fr     = Fraction of technetium Tc 99m remaining after the time of calibration (see Table 3) 
P      = Number of particles in dose to be administered

N      = The number of particles per vial
VTc = The volume of solution added to the reaction vial

Using proper shielding, parenteral drug products should be visually inspected for particulate matter and discoloration prior to administration.

The patient dose should be measured by a suitable radioactivity calibration system immediately prior to administration. Mix the contents of the vial by gentle inversion just prior to withdrawing a patient dose.
Gently mix the contents of the syringe just before injection. If blood is drawn into the syringe, any unnecessary delay prior to injection may lead to clot formation. Slow injection is recommended.
For optimum results and because of rapid lung clearance, it is suggested that the patient be positioned under the imaging apparatus before administration. Lung imaging may begin immediately after intravenous injection of the radiopharmaceutical. Due to high kidney uptake, imaging later than one-half hour after administration will yield poor results.

DIRECTIONS FOR PREPARATION

The preparation of Technetium Tc 99m Albumin Aggregated Injection may be accomplished by the following procedure. Use aseptic procedure throughout and take precautions to minimize radiation exposure by the use of suitable shielding. Waterproof gloves should be worn during the preparation procedure.

Before reconstituting a vial it should be inspected for cracks and/or a melted plug or any other indication that the integrity of the vacuum seal has been lost.

It is anticipated that any Tc 99m generator approved in Canada would be suitable as a source of sodium pertechnetate Tc 99m, however, complete data is not available to confirm this. Jubilant DraxImage Inc. should be contacted for any available information.

The Tc 99m pertechnetate eluate should be less than 2 hours old and should be obtained from a generator which has been eluted within the last 24 hours.

To prepare Technetium Tc 99m Albumin Aggregated Injection:

1.   Remove the protective disc from the reaction vial and swab the closure with an alcohol swab.
2.   Place the vial in a suitable lead vial shield which has a minimum wall thickness of 3 mm (1/8 inch) and a fitted lead cap. Obtain 2 to 8 mL of sterile, non-pyrogenic sodium pertechnetate Tc 99m using a shielded syringe.


The recommended maximum amount of technetium Tc 99m (at the time of elution) to be added to a reaction vial is 5.18 gigabecquerels (140 mCi). Sodium pertechnetate Tc 99m solutions containing an oxidizing agent are not suitable for use.

3.   Using a shielded syringe, aseptically add the sodium pertechnetate Tc 99m solution to the reaction vial, while avoiding the build up of excessive pressure in the vial. Pressure build up may be avoided by injecting several milliliters of pertechnetate solution into the reaction vial, then withdrawing several milliliters of nitrogen gas (present to prevent oxidation of the complex) into the syringe. The procedure is repeated as necessary until the entire amount of pertechnetate is added to the vial and normal pressure is established within the vial.

4.   Place the lead cap on the vial shield and mix the contents of the shielded vial by repeated gentle inversion until all the material is suspended. Avoid the formation of foam. Using proper shielding, the vial should be visually inspected to ensure that the suspension is free of foreign matter before proceeding; if it is not, the radiopharmaceutical should not be used. To ensure maximum radiolabelling, allow the preparation to stand for 15 minutes after mixing at 2° C to 8 °C.
5.    Assay the product in a suitable calibrator, record the radioassay information on the label which has a radiation warning symbol. Also note the time and date of preparation. Apply the label to the vial shield.

6.   The radiochemical purity of the finished preparation should be determined prior to patient administration. The radiochemical purity should not be less than 90%.


7.   Withdrawals for administration must be made aseptically using a sterile needle (18to 21 gauge) and syringe. Since the vials contain nitrogen, the vials should not be vented. If repeated withdrawals are made, the replacement of the contents of the vial with air should be minimized.


8.   The finished preparation should be discarded after 8 hours. It should also be retained during its life in a lead vial shield with the lead cap in place.

Radiochemical Purity

Chromatographic Methods
The following procedure describes a series of simple steps for running chromatograms.
Steps 1to 6 describe the method for determining free pertechnetate in a mixture of chelated and reduced technetium. The TLC procedure requires the following:

Solid phase:    ITLC-SG
Solvent:        Acetone (for determination of pertechnetate)

Step 1

Add 1 mL of the required solvent to an 18 mm x 150 mm test tube. Stopper and allow the atmosphere in the tube to equilibrate for 1 minute.

Step 2

Place a drop (approximately 0.02 mL) of the radioactive solution on a 1 cm x 10 cm chromatographic strip at a pencil mark 1 cm from one end of the strip, which is the origin. A simple way to do this is to use a standard 1 mL tuberculin syringe with a 25 gauge needle and dispense one small drop. Discard the needle and syringe after use. Instead of a tuberculin syringe a 20 microliter disposable micropipette can also be used to dispense 0.02 mL.

Immediately dry the spot using a gentle stream of nitrogen gas. Do not use compressed air since this tends to cause pertechnetate formation.
Step 3

Develop the chromatogram by placing it, with the origin down into the solvent, in the previously equilibrated test tube. Stopper the test tube. The test tube should be kept upright, ideally in a test tube rack. Development requires about 10 minutes for ITLC-SG strips.
Step 4

When the solvent front has climbed to the top of the strip, remove it with forceps and allow it to dry. The strips can be dried by placing them radioactive side up on a disposable non-porous pad at room temperature.

The bound and reduced fractions stay at the origin while free pertechnetate TcO4- migrates to the front Rf 0.85 to 1.0.


Step 5
Cut the dried strip 2 cm from the solvent front end. The short piece is marked Part II and the long piece is marked Part I. Count the pieces in a suitable counter and determine the percentage of free pertechnetate according to the following formula:


Percent TcO4- =               Counts in Part II x 100
Counts in Part I + Part II

Step 6

Store all waste radioactive strips for 48 hours before disposing of them as non-radioactive waste.
Store used chromatographic solvents in a similar fashion.