Technetium Tc99m exametazime scintigraphy (with or without methylene blue stabilization) may be useful as an adjunct in the detection of altered regional cerebral perfusion in stroke.

Tc99m exametazime without methylene blue stabilization is indicated for leukocyte labeled scintigraphy as an adjunct in the localization of intra-abdominal infection and inflammatory bowel disease.

Tc99m labeled leukocytes for adjunctive localization of intra-abdominal infection or inflammation.

The normal adult (70 kg) dose is 0.259-0.925 GBq (7-25 mCi) as Tc99m labeled leukocytes by intravenous injection. Optimal planar imaging is between 2-4 hours. Do not use methylene blue in the preparation of the Tc99m labeled leukocytes (See preparation and handling section).

Cerebral Scintigraphy

The recommended dose range for i.v. administration, of reconstituted sodium pertechnetate Tc99m exametazime (with or without methylene blue) in the average adult (70 kg) is 370-740 MBq (10-20 mCi).

Dynamic imaging may be performed between 0 to 10 minutes following injection. Static imaging may be performed from 15 minutes up to 6 hours after injection.

Instructions For Precautions And Use

General Preparation Precautions

The technetium Tc99m labeling reaction involved in preparing technetium Tc99m exametazime injection depends on maintaining tin in the divalent (reduced) state. Any oxidant present in the sodium pertechnetate Tc99m employed may adversely affect the quality of the preparation. Sodium pertechnetate Tc99m containing oxidants should not be used for the preparation of the labeled product. To meet the last requirement, a generator must be eluted within 24 hours prior to obtaining any elute for reconstitution with the Ceretec (technetium tc99m exametazime injection) kit.

Sodium Chloride Injection, USP must be used as the diluent. Do not use bacteriostatic sodium chloride as a diluent for sodium pertechnetate Tc99m injection because it will increase the oxidation products and adversely affect the biological distribution of Ceretec (technetium tc99m exametazime injection) .

The contents of the Ceretec (technetium tc99m exametazime injection) vial are sterile and pyrogen free. The vial contains no bacteriostatic preservative. It is essential that the user follow the directions carefully and adhere to strict aseptic procedures during preparation of the radiopharmaceutical.

Technetium Tc99m exametazime injection, like other radioactive drugs, must be handled with care and appropriate safety measures should be used to minimize radiation exposure to clinical personnel. Care should also be taken to minimize radiation exposure to the patient consistent with proper patient management.

Care should be taken when handling blood specimens to be labeled using this radiopharmaceutical. Even if the subject has been tested, no method can offer complete assurance that Hepatitis B Virus, Human Immuno-deficiency Virus (HIV) or other infectious agents are absent. All human blood samples should be considered potentially infectious. Precautions for handling are as those for handling radioactive materials.

Procedure for the preparation of Tc99m exametazime with Methylene Blue Stabilizer for intravenous injection use in cerebral scintigraphy

NOTE: DO NOT USE THIS PROCEDURE FOR LEUKOCVTE LABELING. SEE PROCEDURE FOR THE RADIOLABELING OF AUTOLOGOUS LEUKOCYTES WITH TECHNETIUM Tc99m EXAMETAZIME INJECTION.

Note: Sterile technique must be used throughout. The user should wear waterproof gloves during the handling and administration procedure.

1. Withdraw 0.5 ml Methylene Blue Injection USP 1% into a sterile syringe and inject into 4.5 ml vial of 0.003 M Monobasic Sodium Phosphate USP and Dibasic Sodium Phosphate USP in 0.9% Sodium Chloride Injection USP. Gently swirl and withdraw 2 ml of Methylene Blue/Phosphate Buffer mixture into a syringe. This mixture must be used within 30 minutes of preparation.
2. Reconstitute Ceretec (technetium tc99m exametazime injection) with Technetium Tc99m according to the preparation procedure for Preparation of Tc99m Exametazime Injection Without Methylene Blue Stabilizer. 0.37 GBq to 2.0 GBq (10 mCi to 54 mCi) technetium Tc99m may be added to the vial. Immediately proceed to Step 3.
3. Add methylene blue stabilizing solution from Step 1 to the reconstituted Ceretec (technetium tc99m exametazime injection) vial within 2 minutes of reconstitution.
4. Determine the radiochemical purity of the solution (see Radiochemical Purity Measurement section). A radiochemical purity greater than 80% is necessary for product acceptance.
5. Maintain adequate shielding of the radioactive preparation.
6. The injection may be used for up to 4 hours in cerebral scintigraphy studies.
7. Prior to patient injection, attach enclosed syringe filter.
8. The pH of the prepared injection is 6.5-7.5.
9. Also see section on Cautionary Notes for all Preparations.

Procedure for the Preparation of Technetium Tc99m Exametazime Injection Without Methylene Blue Stabilizer

Note: Sterile technique must be used throughout. The user should wear waterproof gloves during the handling and administration procedure.

1. Place one of the vials in a suitable shielding container and swab the rubber septum with the sterile swab provided.
2. Using a 10 ml syringe, inject into the shielded vial 5 ml of sterile eluate from a technetium Tc99m generator (see notes 1-3). Before withdrawing the syringe from the vial, withdraw 5 ml of gas from the space above the solution to normalize the pressure in the vial. Gently invert the shielded vial for 10 seconds to ensure complete dissolution of the powder.
3. Assay the total activity and calculate the volume to be injected. The patient dose should be measured in a suitable radioactivity calibration system immediately prior to administration.
4. Complete the label provided and attach to the vial shield. The technetium Tc99m exametazime injection is ready for quality control.
5. Maintain adequate shielding of the radioactive preparation.
6. Do not use the preparation more than 30 minutes after time of formulation. Discard any unused material.
7. Visually inspect the reconstituted material at a safe distance behind lead glass, and do not use if there is evidence of foreign matter.
8. The injection may be prepared for use in cerebral scintigraphy or for use in the preparation of Tc99m labeled WBCs.
9. The pH of the prepared injection is 9.0-9.8.
10. Also see section on Cautionary Notes for all Preparations.

Procedure for Radiolabeling of Autologous Leukocytes with Technetium Tc99m Exametazime Injection

Note: Sterile technique must be used throughout. The user should wear water proof gloves during the handling and administration procedure.

1. Prepare a 60 ml syringe containing 10 ml acid citrate dextrose solution.
2. Using asepticvenipuncture technique and the prepared syringelfrom Step 1) fitted with a 19 or 20 gauge needle, withdraw approximately 40 ml whole blood from the patient. (Blood withdrawal should be smooth and slow so as not to produce bubbles orfoaming). Cap syringe afterwithdrawing blood.
3. Gently mix the contents of the syringe.
4. Clamp the syringe barrel to the ring stand in an upright (needle side up) position and tilt the syringe 10-20 degrees from its position perpendicularto the bench.
5. Allow the red cells to sediment 30-60 minutes, depending upon when the supernatant [leukocyte rich plasma (LRP)] looks clear of red blood cells.
6. Replace the capped needle with a winged infusion set.
7. Collect the plasma (LRP) into a centrifuge tube marked "WBC" by expressing the LRP through the infusion set tubing assuring the red cells do not enter the container.
8. Immediately centrifuge the capped WBC tube at 400-450 g for 5 minutes.
9. Transfer the supernatant to the leukocyte poor plasma "LPP"tube allowing enough supernatant to cover the white cell button.
   (Note: the button often contains a small number of red cells and may appear red.) Reserve LPP for later use (steps 12,16,19).
10. Wash the white cell button with approximately 5.0 mL Sodium Chloride Injection, USP (0.9%). Cap the tube and resuspend the button by gently swirling.
11. Centrifuge the capped "WBC" tube at 150 g for 8 minutes and discard all but 0.5-1.0 mL of the supernate to cover the cells.
12. Add 1.0 mL of "LPP" to the white cell button and resuspend the cells by gentle swirling.
13. Reconstitute a vial of Ceretec (technetium tc99m exametazime injection) with approximately 30 mCi of Tc99m pertechnetate in 5.0 mL Sodium Chloride (0.9%) Injection, according to the procedure outlined below. Generator eluate more than 2 hours old should not be used. Do not use methylene blue or phosphate buffer.Parenteral drug products should be inspected visually for particulate matter and discoloration before administration.
14. Add the Tc99m Ceretec (technetium tc99m exametazime injection) to the "WBC" tube. Swirl gently to mix.
15. Set a lab timer for 15 minutes and allow the white cells to incubate. Swirl periodically during the incubation.
16. After incubation, withdraw about 10 mL of the LPP and add to the white cell suspension in the "WBC" tube.
17. Cap the "WBC" tube, gently swirl, and then centrifuge at 450 g for 5 minutes.
18. Decant the supernatant in the "WBC" tube into the "Wash" tube and leave the labeled white cells in the "WBC" tube.
19. Add approximately 5 ml of LPP to the "WBC" tube. Resuspend the cells by gentle swirling.
20. When the cells are in suspension, withdraw the cells into a syringe. Cap the syringe and assay the amount of radioactivity in a dose calibrator.
21. Place the syringe in a lead shielded container.
22. Administer the Tc99m labeled leukocyte suspension using a 19G needle as soon as possible after labeling.
23. Also see section of Cautionary Notes for all Preparations.

Cautionary Notes for all Preparations

1. 0.37 GBq up to 2.00 GBq (10 mCi up to 54 mCi) technetium Tc99m may be added to the vial. Before reconstitution the technetium Tc99m generator eluate may be adjusted to the correct radioactive concentration to a volume of 5 ml by dilution with preservative-free, non-bacteriostatic saline for injection.
2. Use only eluate from a technetium Tc99m generator which was previously eluted within 24 hours. For brain imaging when using stabilizing protocol, generator eluate more than 30 minutes old should not be used. For the highest radiochemical purity reconstitute with freshly eluted technetium Tc99m generator eluate. For white blood cell labeling, generator elute more than 2 hours old should not be used.
3. Radiochemical purity testing must be performed prior to patient administration. A radiochemical purity greater than 80% is necessary for product acceptance.
4. Do not use the final radiopharmaceutical preparation forstabilized Ceretec (technetium tc99m exametazime injection) more than 4 hours after the time of reconstitution. Do not use the final radiopharmaceutical preparation for unstabilized Ceretec (technetium tc99m exametazime injection) more than 30 minutes after the time of reconstitution. Discard any unused material.

Quality Control

Radiochemical puritydetermination must be performed before administration to the patient. Three potential radiochemical impurities may be present in the prepared injection of the lipophilic technetium Tc99m exametazime complex.

These are a secondary technetium Tc99m exametazime complex, free pertechnetate, and reduced-hydrolyzed-technetium Tc99m. A combination of 3 chromatographic systems is necessary for the complete definition of the radiochemical composition of the injection.

Thefollowing protocol has been designed to enableanalysis of the radiochemical purity of Ceretec (technetium tc99m exametazime injection) (99mTc-exametazime). It should be started within 2 minutes of reconstitution. The entire procedure takes approximately 15 minutes.

Equipment and Eluents

1. Quality control kit which includes all necessary components (available from BIODEX Medical Systems Inc./ Phone # 516-924-9000 - Cat. #151-660).
2. Individual supplies:
   
   Gelman ITLC/SG strips6 cmxO.7 cm (availablefrom BIODEX Medical Systems Inc./Phone # 516-924-9000 - Black Strip)
   Whatman strips 6 cm x 0.7 cm (available from BIODEX Medical Systems Inc./Phone # 516-924-9000 - Red Strip)
   MEK (methyl ethyl ketone [butanone])(Aldrich Cat. #27069-5,99.9 + % HPLC Grade)
   0.9% aqueous sodium chloride (non-bacteriostatic)
   50% aqueous acetonitrile (Aldrich Cat. #27071-7, 99.9 + % HPLC Grade)
   Dilute with non-bacteriostatic Water for Injection
   Glass test tubes (12 x 75 mm)
   1 ml syringes with 25 gauge needles
   
   
3. Suitable counting equipment.

Method

1. Prepare three chromatography tubes containing 0.2-0.3 ml of fresh MEK, 0.9% sodium chloride and 50% acetonitrile, respectively. Identify the solvent in each tube.
2. Prepare two ITLC/SG (black) strips and one Whatman paper (red) strip. Each is marked by the manufacturer 1.0cm from the bottom as the point of origin.
3. Reconstitute a Ceretec (technetium tc99m exametazime injection) vial according to this insert.
4. Apply at least 5 µL samples of Ceretec (technetium tc99m exametazime injection) to the origin of the three strips within 15 minutes of reconstitution. Immediately place one ITLC/SG (black) strip into the MEK tube, the second ITLC/SG (black) strip into the saline tube and the paper (red) strip into the 50% acetonitrile tube. Make sure strips are not adhering to the side of the test tube.
5. The ITLC/SG MEK (black) strip takes approximately 45 seconds to run. When the eluate has reached the solvent front remove the strip from the tube with forceps and immediately cut 1.0 cm above the origin.
6. The ITLC/SG saline(black)striptakes approximately 45 seconds to run. When the eluate has reached the solvent front remove the strip from the tube with forceps and immediately cut 2.5 cm above the origin.
7. The Whatman paper CI₃CN (red) strip takes approximately 100 seconds to run. When the eluate has reached the solvent front remove the stripfrom the tube with forceps and immediately cut 0.5 cm above the origin.
8. Count the separate sections of each strip to determine the activity distribution. Make sure proper counting geometry is maintained attempting to reduce any interference from equipment dead time.
9. Determine:
   % bottom of saline strip - % bottom of MEK strip
   (= % lipophilic exametazime complex)
   % top of saline strip (= % pertechnetate)
   % bottom of Whatman paper strip (= % reduced-hydrolyzed-Tc)

A radiochemical purity of > 80% may be expected provided the measurement has been carried out within 4 hours of reconstitution for stabilized Ceretec (technetium tc99m exametazime injection) and 30 minutes for Ceretec (technetium tc99m exametazime injection) used for WBC labeling.

Interpretation of Chromatogram

System 1 (ITLC: MEK [butanone])

Secondary Tc exametazime complex and reduced-hydrolyzed-Tc remain at the origin.

Lipophilic Tc exametazime complex and pertechnetate migrate at R_f 0.8-1.0.

System 2 (ITLC: 0.9% sodium chloride)

Lipophilic-Tc exametazime complex, secondary Tc exametazime complex and reduced-hydrolyzed-Tc remain at the origin. Pertechnetate migrates at R_f 0.8-1.0.

System 3 (Whatman 1:50% aqueous acetonitrile)

Reduced-hydrolyzed-Tc remains at the origin. Lipophilic Tc exametazime complex, secondary Tc exametazime complex and pertechnetate migrate at R_f 0.8-1.0.

Radiation Dosimetry

Based on human data, the absorbed radiation doses to an average human adult (70 kg) from an intravenous injection of this product are estimated below. The values are listed as µGy/MBq, rads/mCi with urination every 2 hours. Bladderwall dose is 19 µGy/MBq, 0.07 rads/mCi with 4 hour urination and 89 µGy/MBq, 0.33 rads/mCi with no urination.

Table 4. Estimated Absorbed Radiation Dose* for Cerebral Scintigraphy

Table 5.In vivo Localization of Tc99m Labeled Leukocytes
The estimated absorbed radiation doses to various organs following the intravenous administration of Tc99m labeled leukocytes given by ICRP 53** are as follows (bladder voiding every 3.5 hours)

The kit comprises five individual vials of sterile, non-pyrogenic, freeze-dried mixture of exametazime, stannous chloride dihydrate and sodium chloride, ten radiation labels, six sterile alcohol swabs, five radiochemical purity worksheets, five labeling efficiency worksheets, one package insert, five individual vials of Methylene Blue Injection USP 1%, five individual vials of 0.003 M Monobasic Sodium Phosphate USP and Dibasic Sodium Phosphate USP in 0.9% Sodium Chloride Injection USP and fifteen 0.45 µM syringe filters.

NDC 17156-023-05

Storage

Store the kit at 15°-25°C (59°-77°F).

Store the formulated drug at 20°-25°C (68°-77°F) using appropriate radiation shielding. Do not freeze.

This reagent kit is approved for use by persons licensed by the Illinois Emergency Management Agency pursuant to 32 III. Code Adm. Section, Section 330.260(a) and 335.4010 or under equivalent licenses of the U.S. Nuclear Regulatory Commission, or an Agreement State.

Distributed by: GE Healthcare Medi-Physics, Inc. Arlington Heights, IL 60004. Customer Service: 1-800-292-8514. Professional Services: 1-800-654-0118. Manufactured by: GE Healthcare Ltd. Little Chalfont Buckinghamshire, HP7 9NA United Kingdom. FDA Rev date: 6/15/2005

Last reviewed on RxList: 1/21/2009
This monograph has been modified to include the generic and brand name in many instances.