Technetium tc-99m exametazime and cobaltous chloride

Renal Impairment This drug is known to be substantially excreted by the kidney, and radiation exposure may be greater in patients with impaired renal function. A reduction in administered Tc 99m can be considered provided an adequate number of leukocytes are administered.

Important Preparation and Radiation Safety Instructions The Ceretec kit includes a cobalt stabilizer solution, which is optional for cerebral scintigraphy. DO NOT USE COBALT STABILIZER SOLUTION FOR LEUKOCYTE LABELED Scintigraphy [see Dosage and Administration (2.4 , 2.6) ] . Technetium Tc 99m exametazime injection is a radioactive drug and should be handled with appropriate safety measures to minimize radiation exposure [see Warnings and Precautions ] .

Use waterproof gloves and effective shielding, including syringe shields, when preparing and administering technetium Tc 99m exametazime injection.

Preparation and Administration Instructions General Preparation and Administration Instructions Use aseptic procedures throughout preparation and handling. Visually inspect the reconstituted technetium Tc 99m exametazime injection prior to use and do not use if there is evidence of particulate matter or discoloration. Measure patient dose with a dose calibrator immediately prior to administration.

Instruct patients to maintain adequate hydration, after administration of technetium Tc 99m exametazime labeled white blood cells or Tc 99m exametazime injection and void frequently to minimize radiation dose to the kidneys and bladder [see Warnings and Precautions ]. Reconstitution Instructions Elute the technetium Tc 99m generator according to the manufacturer's instructions.

Only use eluate from a technetium Tc 99m generator which has been eluted within the previous 24 hours. For the highest radiochemical purity reconstitute with freshly eluted technetium 99m generator eluate. To prepare technetium Tc 99m exametazime injection for white blood cell labeling , use generator elute that is not more than 2 hours old.

To prepare technetium Tc 99m exametazime injection with cobalt stabilizer for cerebral imaging , use generator eluate that is not more than 4 hours old.

Preparation of Autologous Leukocytes Leukocyte Harvest and Separation 1) Draw up 10 mL acid citrate dextrose solution into a 60 mL syringe. 2) Withdraw approximately 40 mL whole blood from the patient into the syringe using a 19-gauge butterfly needle infusion set. Close the syringe with a sterile hub. 3) Gently mix the contents of the syringe for 20 seconds. 4) Clamp the syringe barrel to the ring stand in an upright (hub side up) position and tilt the syringe 10-20 degrees from its position perpendicular to the bench. 5) Allow the red cells to sediment 30-60 minutes, until the supernatant [leukocyte rich plasma (LRP)] looks clear of red blood cells. 6) Using an infusion set, transfer the leukocyte-rich plasma (LRP), the supernatant, from the previous step, into a sterile, conical centrifuge tube marked "WBC" (white blood cell) and assure that only a minimum amount of red cells enter the centrifuge tube. 7) Immediately centrifuge the capped WBC tube at 400-450 g for 5 minutes.

The plasma will separate out into a liquid [leukocyte poor plasma (LPP)] and a solid (WBC button). (Note: The button often contains a small number of red cells and may appear red). 8) Transfer the supernatant into another sterile tube marked "LPP" leaving enough supernatant to cover the white cell button. Reserve LPP for later use (steps 11,15,18).

Washing and Radiolabeling 9) Add approximately 5 mL Sodium Chloride Injection, USP (0.9%) to the WBC button. Cap the "WBC" tube and resuspend the button by gently swirling. 10) Centrifuge the capped "WBC" tube at 150 g for 8 minutes and discard all but 0.5 to 1 mL of the supernatant to cover the cells. 11) Add 1 mL of "LPP" (from Step 9) to the white cell button and resuspend the cells by gentle swirling. 12) Reconstitute technetium Tc 99m exametazime from Ceretec with generator eluate [see Dosage and Administration ] . 13) Within 30 minutes of preparation, add the reconstituted Tc 99m exametazime (do not use cobalt stabilizer solution) to the "WBC" tube.

Swirl gently to mix. 14) Set a lab timer for 15 minutes and allow the white cells to incubate. Swirl at 30 second intervals during the incubation. 15) After incubation, add 10 mL of the LPP (from Step 9) to the "WBC" tube. 16) Cap the "WBC" tube, gently swirl, and then centrifuge at 450 g for 5 minutes. 17) Transfer the supernatant in the "WBC" tube into the "Wash" tube and leave the labeled white cells in the "WBC" tube. 18) Add approximately 5 mL of LPP (from Step 9) to the "WBC" tube.

Gently swirl to resuspend the cells. 19) Draw the labeled cells into a syringe. Cap the syringe and assay the amount of radioactivity in a dose calibrator. Place the syringe in a shielded container. 20) Verify the identity of the labeled leukocyte recipient. 21) Administer the Tc 99m labeled leukocyte suspension using a 19G needle as soon as possible, preferably within 1-2 hours after labeling.

Preparation of Tc 99m Exametazime Injection with Cobalt Stabilizer Solution The preparation may be used in cerebral scintigraphy 1) Add up to 370 MBq to 2000 MBq (10 mCi to 54 mCi) sodium pertechnetate Tc 99m eluate to the shielded Ceretec vial. 2) Before reconstitution, the technetium Tc 99m generator eluate may be adjusted to the correct radioactive concentration [74 to 400 MBq/mL (2 to 10.8 mCi/mL)] by dilution with a volume of 5 mL preservative-free, non-bacteriostatic 0.9% sodium chloride for injection. 3) Between 1 and 5 minutes after reconstitution, inject 2 mL of cobalt stabilizer solution into the vial.

Shake the shielded vial for 10 seconds to ensure complete mixing. 4) The cobalt stabilized technetium 99m exametazime is a pale straw-colored solution and the pH is in the range 5 to 8. 5) Use a Sample for Radiochemical Purity measurement. 6) Assay the vial for total radioactivity. Calculate the volume to be injected. Complete the label provided and attach to the vial. 7) Use the stabilized product within 5 hours after preparation.

Individual patient doses may be stored aseptically in a capped syringe if required. 8) Discard any unused material. Radiochemical Purity Measurement Tc 99m Exametazime Injection with Cobalt Stabilizer Solution Obtain the Following Materials: Two GMCP-SA (Glass Microfiber Chromatography Paper impregnated with Silicic Acid) strips (2 cm (±2 mm) × 20 cm) Ascending chromatography development tanks MEK [methyl ethyl ketone (butanone)] 0.9 % sodium chloride A combination of two chromatographic systems is necessary for the determination of the radiochemical purity of the injection: System 1 GMCP-SA: MEK [methyl ethyl ketone (butanone)] System 2 GMCP-SA:0.9% sodium chloride Three potential radiochemical impurities may be present in prepared Technetium ( 99m Tc) Exametazime Injection secondary Tc 99m exametazime complex free Tc 99m pertechnetate reduced-hydrolyzed Tc 99m Method 1) Perform radiochemical purity testing as soon as possible after preparation. 2) Prepare the two Chromatographic Systems (System 1 and System 2). 3) Apply test samples by needle approximately 2.5 cm from the bottom of each GMCP-SA strip. 4) Immediately place each strip in prepared ascending chromatography development tanks.

After the solvent has travelled to the 14 cm mark, remove the strips and mark the solvent fronts. 5) Allow the strips to dry. 6) Determine the distribution of activity determined using suitable equipment. 7) Chromatogram Interpretation: [See table below.] [See table below.] 8) Calculate the percentage of activity due to both secondary Tc 99m exametazime complex and reduced-hydrolyzed Tc 99m from System 1 (A %) . 9) Calculate the percentage of activity due to Tc 99m pertechnetate from System 2 (B %) . 10) Calculate the radiochemical purity: % lipophilic Tc 99m exametazime complex = 100 - (A %+B %) A % represents the level of secondary Tc 99m exametazime complex plus reduced-hydrolyzed Tc 99m.

B % represents the level of Tc 99m pertechnetate. 11) Do not use if radiochemical purity of lipophilic Tc 99m exametazime is less than 80%.

Preparation of Technetium Tc 99m Exametazime Injection Without Cobalt Stabilizer Solution The preparation may be used in cerebral scintigraphy or for use in the preparation of Tc 99m labeled leukocytes. 1) Add 370 MBq to 2000 MBq (10 mCi up to 54 mCi) of sodium pertechnetate Tc 99m eluate. 2) Before reconstitution, the technetium Tc 99m generator eluate may be adjusted to the correct radioactive concentration [74 to 400 MBq/mL (2 to 10.8 mCi/mL)] by dilution with a volume of 5 mL preservative-free, non-bacteriostatic 0.9 % sodium chloride for injection. 3) The pH of the prepared injection is 9 to 9.8. 4) Use a sample for Radiochemical Purity Measurement. 5) Assay the total activity. 6) Calculate the volume to be injected and complete the label provided and attach to the vial shield. 7) Use the preparation within 30 minutes after reconstitution. 8) Discard any unused material.

Radiochemical Purity Measurement Tc 99m Exametazime Injection without Cobalt Stabilizer Solution Perform radiochemical purity testing of technetium Tc 99m exametazime within 2 minutes of reconstitution. The entire procedure takes approximately 15 minutes. Obtain the Following Materials: 2 SA ITLC strips 20 cm × 2 cm 1 Whatman No. 1 strips 6 cm × 0.7 cm MEK (methyl ethyl ketone [butanone]) 0.9% aqueous sodium chloride (non-bacteriostatic) 50% aqueous acetonitrile Dilute with non-bacteriostatic Water for Injection Glass test tubes (12 × 75 mm) Glass measuring cylinders (100 mL) with covers 1 mL syringes with 25-gauge needles A combination of 3 chromatographic systems is necessary for the complete definition of the radiochemical composition of the injection.

System 1 : MEK (methyl ethyl ketone [butanone]) + SA ITLC strip System 2 : 0.9% non-bacteriostatic sodium chloride solution + SA ITLC strip System 3 : 50% acetonitrile solution + Whatman No. 1 paper strip Three potential radiochemical impurities may be present in the prepared injection of the lipophilic Tc 99m exametazime complex. a secondary Tc 99m exametazime complex free Tc 99m pertechnetate reduced-hydrolyzed Tc 99m Method 1) Prepare chromatography tubes (Identify the solvent in each cylinder).

System 1 - 100 mL cylinder containing a 1 cm depth of fresh MEK. System 2 - 100 mL cylinder containing a 1 cm depth of 0.9% sodium chloride. System 3 - 1 chromatography tube containing 0.2-0.3 mL of 50% acetonitrile, respectively. 2) Prepare 2 SA ITLC strips and 1 Whatman No. 1 paper strip. Mark the SA ITLC strips 2.5 cm from the bottom as the point of origin.

Mark both the SA ITLC strips at 14 cm above the origin (solvent front). Mark the Whatman strip 1 cm from the bottom as the point of origin. 3) Apply at least 5 microliter samples of freshly prepared Tc 99m exametazime solution to the origin of the 3 strips (within 2 minutes of reconstitution). Do not allow to dry. 4) Immediately place 1 SA ITLC strip into the MEK tank (System 1), the second SA ITLC strip into the saline tank (System 2), and the Whatman No. 1 paper strip into the 50% acetonitrile tube (System 3). 5) The SA ITLC MEK strip takes approximately 15 minutes to run.

When the eluate has reached the solvent front remove the strip from the tube with forceps and immediately cut 1 cm above the origin. 6) The SA ITLC saline strip takes approximately 15 minutes 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 No. 1 paper CH3CN strip takes approximately 100 seconds to run.

When the eluate has reached the solvent front mark remove the strip from the tube with forceps and immediately cut 0.5 cm above the origin. 8) Chromatogram Interpretation: [See table below.] [See table below.] [See table below.] 9) Count the separate sections of each strip to determine the activity distribution. Calculate: % origin of saline strip (system 2) % origin of MEK strip (system 1) % solvent front of saline strip (= % Tc 99m pertechnetate) % origin of Whatman No. 1 paper strip (= % reduced-hydrolyzed Tc 99m) 10) Calculate Radiochemical Purity % lipophilic Tc 99m exametazime complex = % origin of saline strip (system 2) – % origin of MEK strip (system 1) 11) Do not use if the radiochemical purity of the lipophilic Tc 99m exametazime complex is less than 80%.