Ceretec Dosage

Leukocyte Labeled Scintigraphy

Cerebral Scintigraphy

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 (5.3)].

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.

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 (2.6)].

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.

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 (99mTc) Exametazime Injection

• secondary Tc 99m exametazime complex
• free Tc 99m pertechnetate
• reduced-hydrolyzed Tc 99m

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

Tc 99m Exametazime labeled leukocytes for leukocyte labeled scintigraphy

Radiation absorbed dose per unit activity (microGy/MBq) administered to average-size adults (70 kg) and pediatric patients from an intravenous injection of Tc 99m Exametazime labeled leukocytes is estimated in Table 1.

Tc 99m Exametazime Injection for Cerebral Scintigraphy

Based on human data, the radiation absorbed doses to average sized adults (70kg) and pediatric patients from an intravenous injection of Tc 99m exametazime injection are estimated in Table 2.

The effective dose resulting from the administration of a (maximal recommended) activity of 1110 MBq for an adult weighing 70 kg is about 10.3 mSv. For an administered activity of 740 MBq the typical radiation dose to the target organ (brain) is 5 mGy and the typical radiation dose to the critical organ (kidneys) is 25 mGy.