Gozetotide

The effective radiation dose resulting from the administration of 259 MBq (7 mCi) is 4.4 mSv. The radiation doses for this administered dose to the critical organs, which are the kidneys, urinary bladder, and spleen, are 96.2 mGy, 25.4 mGy, and 16.8 mGy, respectively. These radiation doses are for gallium Ga 68 gozetotide injection alone.

Radiation Safety – Drug Handling After reconstitution and radiolabeling of LOCAMETZ, the vial contains gallium Ga 68 gozetotide injection. Handle the gallium Ga 68 gozetotide injection with appropriate safety measures to minimize radiation exposure [see Warnings and Precautions] . Use waterproof gloves, effective radiation shielding, and other appropriate safety measures when preparing and handling gallium Ga 68 gozetotide injection.

Radiopharmaceuticals should be used by or under the control of health care providers who are qualified by specific training and experience in the safe use and handling of radionuclides, and whose experience and training have been approved by the governmental agency authorized to license the use of radionuclides.

Patient Preparation Advise patients to be well hydrated prior to gallium Ga 68 gozetotide injection administration and to void immediately prior to and frequently during the first hours after image acquisition to reduce radiation exposure [see Warnings and Precautions] .

Drug Preparation LOCAMETZ allows the direct preparation of gallium Ga 68 gozetotide injection with the eluate from one of the following generators (see below for specific instruction 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 instructions for use provided by the germanium-68/gallium-68 generator manufacturer should also be followed.

Prepare gallium Ga 68 gozetotide injection according to the following aseptic procedure: a. Use suitable shielding to reduce radiation exposure. b. Wear waterproof gloves. c. Flip the cap off the LOCAMETZ vial and swab the septum with an appropriate antiseptic, then allow the septum to dry. d. Pierce the LOCAMETZ vial septum with a sterile needle connected to a 0.2-micron sterile air venting filter to maintain atmospheric pressure within the vial during the reconstitution process. e.

Place the LOCAMETZ vial in a lead shield container. f. Follow the generator specific procedures below. Schematic diagrams are provided in Figures 1 and 2. Preparation with Eckert & Ziegler GalliaPharm Generator 1) Connect the male luer of the outlet line of the generator to a sterile elution needle (size 21G to 23G). 2) Connect the LOCAMETZ vial directly to the outlet line of the generator by pushing the elution needle through the rubber septum. 3) Elute directly from the generator into the LOCAMETZ vial. 4) Perform the elution manually or by means of a pump according to the generator instructions for use. 5) Reconstitute the lyophilized powder with 5 mL of eluate. 6) At the end of the elution, disconnect the LOCAMETZ vial from the generator by removing the elution needle and the vent needle with the 0.2-micron sterile air venting filter from the rubber septum.

Then, invert LOCAMETZ vial once and place it upright. 7) Incubate the LOCAMETZ vial upright between 20°C to 30°C (68°F to 86°F) for at least 5 minutes without agitation or stirring. 8) After 5 minutes, assay the vial containing the gallium Ga 68 gozetotide injection for total radioactivity using a dose calibrator, calculate the radioactivity concentration and record the result. 9) After radiolabeling, gallium Ga 68 gozetotide injection may be diluted with Sterile Water for Injection, USP or 0.9% Sodium Chloride Injection, USP up to a final volume of 10 mL. 10) Perform quality controls according to the recommended methods in order to check compliance with the specifications [see Dosage and Administration] . 11) Store the LOCAMETZ vial containing the gallium Ga 68 gozetotide injection upright in a lead shield container below 30°C (86°F) until use. 12) After addition of gallium-68 chloride to the LOCAMETZ vial, use gallium Ga 68 gozetotide injection within 6 hours.

Preparation with IRE ELiT Galli Eo Generator 1) Connect the male luer of the outlet line of the generator to a sterile elution needle (size 21G to 23G). 2) Connect the LOCAMETZ vial directly to the outlet line of the generator by pushing the elution needle through the rubber septum. 3) Connect the LOCAMETZ vial through the vent needle with 0.2-micron sterile air venting filter to a vacuum vial (25 mL minimum volume) by means of a sterile needle (size 21G to 23G) or to a vacuum pump to start the elution. 4) Elute directly from the generator into the LOCAMETZ vial. 5) Reconstitute the lyophilized powder with 1.1 mL of eluate. 6) At the end of the elution, first withdraw the sterile needle from the vacuum vial or disconnect the vacuum pump in order to establish atmospheric pressure into the LOCAMETZ vial, then disconnect the vial from the generator by removing both the elution needle and the vent needle with the 0.2-micron sterile air venting filter needle from the rubber septum.

Inversion of the LOCAMETZ vial is not needed. 7) Incubate the LOCAMETZ vial upright between 20°C to 30°C (68°F to 86°F) for at least 5 minutes without agitation or stirring. 8) After 5 minutes, assay the vial containing the gallium Ga 68 gozetotide injection for total radioactivity using a dose calibrator, calculate the radioactivity concentration and record the result. 9) After radiolabeling, gallium Ga 68 gozetotide injection may be diluted with Sterile Water for Injection, USP or 0.9% Sodium Chloride Injection, USP up to a final volume of 10 mL. 10) Perform quality controls according to the recommended methods in order to check compliance with the specifications [see Dosage and Administration] . 11) Store the LOCAMETZ vial containing the gallium Ga 68 gozetotide injection upright in a lead shield container below 30°C (86°F) until use. 12) After addition of gallium-68 chloride to the LOCAMETZ vial, use gallium Ga 68 gozetotide injection within 6 hours.

Figure 1. Preparation with Eckert & Ziegler GalliaPharm Generator Figure 2. Preparation with IRE ELiT Galli Eo Generator

Administration a. Use aseptic technique and radiation shielding when withdrawing and administering gallium Ga 68 gozetotide injection. b. Calculate the necessary volume to administer based on calibration time and required dose. c. Inspect the prepared gallium Ga 68 gozetotide injection for particulate matter and discoloration behind a lead glass shield for radioprotection purposes.

Use only solutions that are clear, colorless and free from particulate matter. d. Using a single-dose syringe fitted with a sterile needle (size 21G to 23G) and protective shielding, aseptically withdraw the prepared gallium Ga 68 gozetotide injection. e. Verify the total radioactivity in the syringe with a dose calibrator immediately before and after gallium Ga 68 gozetotide injection administration to the patient.

The dose calibrator must be calibrated with NIST traceable standards. f. After injection of gallium Ga 68 gozetotide, administer an intravenous flush of sterile 0.9% Sodium Chloride Injection, USP to ensure full delivery of the dose. g. Dispose of any unused gallium Ga 68 gozetotide injection in a safe manner in compliance with applicable regulations. h.

If clinically necessary, a diuretic expected to act within the uptake time period may be administered at the time of radiotracer injection to potentially decrease artifact from radiotracer accumulation in the urinary bladder and ureters.

Image Acquisition Begin PET scanning 50 minutes to 100 minutes after the intravenous administration of gallium Ga 68 gozetotide injection. Patients should void immediately prior to image acquisition and image acquisition should begin at the mid-thighs and proceed cranially to the skull base or skull vertex. Adapt imaging technique according to the equipment used and patient characteristics in order to obtain the best image quality possible.