68ga-dotatate

The radiation effective dose resulting from the administration of 150 MBq (4.05 mCi) [within the range of the recommended gallium Ga 68 dotatate injection dose] to an adult weighing 75 kg, is about 3.15 mSv. For an administered activity of 150 MBq (4.05 mCi) the typical radiation absorbed dose to the critical organs, which are the urinary bladder wall, the spleen, the kidneys and the adrenals, are about 15 mGy, 16 mGy, 14 mGy and 13 mGy, respectively.

Because the spleen has one of the highest physiological uptakes, higher uptake and radiation dose to other organs or pathologic tissues may occur in patients with spleen disorders (e.g., splenectomy and/or splenosis) [see Warnings and Precautions] . Physical data Gamma constant: 0.67 mrem/hr per mCi at 1 meter [1.8E-4 mSv/hr per MBq at 1 meter] Specific Activity: 4.1E7 Ci/g [1.51E18 Bq/g] max [See table below.] Heart wall 0.018 0.003 Kidneys 0.093 0.016 Liver 0.05 0.015 Lungs 0.006 0.001 Muscle 0.012 0.002 Ovaries 0.016 0.001 Pancreas 0.015 0.002 Red marrow 0.015 0.003 Osteogenic cells 0.021 0.005 Skin 0.01 0.002 Spleen 0.109 0.058 Testes 0.01 0.001 Thymus 0.012 0.002 Thyroid 0.011 0.002 Urinary bladder wall 0.098 0.048 Uterus 0.015 0.002 Total body 0.014 0.002 Effective dose per injection activity mSv/MBq 0.021 0.003 [See table below.] Table 4 indicates how effective dose per injection activity scales with body habitus in computational models of adult and pediatric patients.

Recommended Dosage and Administration Instructions In adults and pediatric patients, the recommended amount of radioactivity to be administered for PET imaging is 2 MBq/kg (0.054 mCi/kg) of body weight up to 200 MBq (5.4 mCi) by intravenous injection (bolus). Verify the injected radioactivity by measuring the radioactivity of the syringe containing the gallium Ga 68 dotatate injection with a dose calibrator before administration to the patient [see Dosage and Administration].

Ensure that the injected radioactivity is within ± 10% of the recommended activity.

Drug Preparation The NETSPOT kit is supplied as 2 vials [see Dosage Forms and Strengths] which allows for direct preparation of gallium Ga 68 dotatate injection with the eluate from one of the following generators (see below for specific instructions for use with each generator): Eckert & Ziegler GalliaPharm germanium-68/gallium-68 ( 68 Ge/ 68 Ga) generator IRE ELiT Galli Eo germanium-68/gallium-68 ( 68 Ge/ 68 Ga) generator The 68 Ge/ 68 Ga generators are not supplied with the NETSPOT kit.

Components of the kit: Vial 1 (reaction vial with lyophilized powder) contains: 40 mcg dotatate, 5 mcg 1,10-phenanthroline; 6 mcg gentisic acid; 20 mg mannitol. Vial 2 (buffer vial) contains: 60 mg formic acid; 56.5 mg sodium hydroxide and water for injection. Ancillary supplies (not included in the kit): Ancillary supplies needed (not supplied in kit): 1 mL sterile plastic syringe, 5 mL sterile plastic syringe, non-metallic or silicone coated sterile needles (size 21 to 23G), 0.2 micron sterile vented filter.

Prepare gallium Ga 68 dotatate injection according to the following aseptic procedure: a. Use suitable shielding to reduce radiation exposure. b. Wear waterproof gloves. c. Test periodically (weekly) the gallium-68 chloride eluate for germanium-68 breakthrough by suitable method. Germanium-68 breakthrough and other gamma emitting radionuclides should be ≤ 0.001%. d.

Set the temperature of the shielded dry bath to 95°C (203°F) and wait for the temperature to reach the set point and stabilize. e. Prepare syringes for elution and radiolabeling steps per Table 1 below. f. Use non-metallic or silicone coated needles to minimize trace metal impurity levels. Radiolabeling of carrier molecules with gallium-68 chloride is very sensitive to the presence of trace metal impurities. g.

Use 1 mL low dead space plastic syringe to precisely measure the adequate volume of reaction buffer to be added during preparation. Do not use glass syringe. h. Prior to piercing vial septums, flip the cap off and swab the top of the vial closure with alcohol to disinfect the surface, and allow the stopper to dry. [See table below.] Solutions for use with IRE Galli Eo generator 5 mL sterile plastic syringe 3.9 mL sterile water for injection For preliminary dilution of Vial 1 1 mL sterile plastic syringe Vial 2 buffer Calculate the volume (in mL) by multiplying the volume of HCl used for the elution of the generator in mL by its molarity: Reaction buffer volume in mL = HCl volume in mL x HCl molarity (1.1 mL x

Administration Prior to use, visually inspect the prepared gallium Ga 68 dotatate injection behind a lead glass shield for radioprotection purposes. Only use solutions that are clear without visible particles. Using a single-dose syringe fitted with a sterile needle (size 21G to 23G) and protective shielding, aseptically withdraw the prepared gallium Ga 68 dotatate injection prior to administration.

Measure the total radioactivity in the syringe by a dose calibrator immediately prior to administration. The dose calibrator must be calibrated with National Institute of Standards and Technology (NIST) traceable standards. Accidental extravasation may cause local irritation due to the acidic pH of the gallium Ga 68 dotatate injection.

In case of extravasation, the injection must be stopped, the site of injection must be changed and the affected area should be irrigated with 0.9% Sodium Chloride Injection, USP. Handle and dispose radioactive material in accordance with applicable regulations.