GALLIUM GA-68 PSMA-11

11.1 Chemical Characteristics Gallium Ga 68 Gozetotide Injection is a radioactive diagnostic agent for intravenous administration. It contains 5 mcg gozetotide, 18.5 MBq/mL to 185 MBq/mL (0.5 mCi/mL to 5 mCi/mL) of gallium Ga 68 gozetotide at calibration time, 1 mL ethanol, 1 mL water for injection, and 10 mL of 0.9% sodium chloride solution (approximately 12 mL total volume). Gallium Ga 68 Gozetotide Injection is provided as a sterile, pyrogen free, clear, colorless solution for intravenous use, with a pH between 4.0 and 7.0. Gozetotide is also known as PSMA-11. Gallium Ga 68 gozetotide is a urea based peptidomimetic that has a covalently bound chelator (HBED-CC). The peptide has the amino acid sequence Glu-NH-CO-NH-Lys(Ahx)-HBED-CC. Gallium Ga 68 gozetotide has a molecular weight of 1011.91 g/mol and its chemical structure is shown in Figure 1. Figure 1: Chemical Structure of Gallium Ga 68 Gozetotide Chemical Structure 11.2 Physical Characteristics Gallium-68 (Ga 68) decays with a half-life of 68 minutes to stable zinc-68. Table 2 and Table 3 display the principal radiation emission data and physical decay of Ga 68. Table 2: Principal Radiation Emission Data (>1%) for Gallium Ga 68 Radiation/ Emission % Disintegration Mean Energy (MeV) beta+ 88% 0.8360 beta+ 1.1% 0.3526 gamma 178% 0.5110 gamma 3.0% 1.0770 X-ray 2.8% 0.0086 X-ray 1.4% 0.0086 Table 3: Physical Decay Chart for Gallium Ga 68 Minutes Fraction Remaining 0 1 15 0.858 30 0.736 60 0.541 90 0.398 120 0.293 180 0.158 240 0.086 360 0.025 11.3 External Radiation Table 4 displays the radiation attenuation by lead shielding of Ga 68. Table 4: Radiation Attenuation of 511 keV Photons by Lead (Pb) Shielding Shield Thickness (Pb) mm Coefficient of Attenuation 6 0.5 12 0.25 17 0.1 34 0.01 51 0.001

Gallium Ga 68 Gozetotide Injection is indicated for positron emission tomography (PET) of prostate-specific membrane antigen (PSMA) positive lesions in men with prostate cancer: with suspected metastasis who are candidates for initial definitive therapy. with suspected recurrence based on elevated serum prostate-specific antigen (PSA) level. Gallium Ga 68 Gozetotide Injection is a radioactive diagnostic agent indicated for positron emission tomography (PET) of prostate-specific membrane antigen (PSMA) positive lesions in men with prostate cancer: with suspected metastasis who are candidates for initial definitive therapy. with suspected recurrence based on elevated serum prostate-specific antigen (PSA) level. (1 )

Use appropriate aseptic technique and radiation safety handling measures to maintain sterility during all operations involved in the manipulation and administration of Gallium Ga 68 Gozetotide Injection. ( 2.1 ) The recommended adult dose is 111 MBq to 259 MBq (3 mCi to 7 mCi) as a bolus intravenous injection. ( 2.2 ) A diuretic expected to act within the uptake time period may be administered at the time of radiotracer injection. ( 2.2 ) Initiate imaging 50 to 100 minutes after administration. The patient should void immediately prior to initiation of imaging. Scan should begin caudally and proceed cranially. ( 2.4 ) See full prescribing information for additional preparation, administration, imaging, and radiation dosimetry information. ( 2 ) 2.1 Radiation Safety – Drug Handling Handle Gallium Ga 68 Gozetotide Injection with appropriate safety measures to minimize radiation exposure [see Warnings and Precautions (5.2) ] . 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 physicians 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 appropriate governmental agency authorized to license the use of radionuclides. 2.2 Recommended Dosage and Administration Instructions Recommended Dosage In adults, the recommended amount of radioactivity to be administered for PET is 111 MBq to 259 MBq (3 mCi to 7 mCi) administered as an intravenous bolus injection. Administration Use aseptic technique and radiation shielding when withdrawing and administering Gallium Ga 68 Gozetotide Injection. Calculate the necessary volume to administer based on calibration time and required dose. Inspect Gallium Ga 68 Gozetotide Injection visually for particulate matter and discoloration before administration. Do not use the drug if the solution contains particulate matter or is discolored. Gallium Ga 68 Gozetotide Injection may be diluted with sterile 0.9% Sodium Chloride Injection, USP. Assay the final dose immediately before administration to the patient in a dose calibrator. After injection of Gallium Ga 68 Gozetotide Injection, administer an intravenous flush of sterile 0.9% Sodium Chloride Injection, USP to ensure full delivery of the dose. Dispose of any unused drug in a safe manner in compliance with applicable regulations. Unless contraindicated, 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. 2.3 Patient Preparation Prior to PET Imaging Instruct patients to drink a sufficient amount of water to ensure adequate hydration prior to administration of Gallium Ga 68 Gozetotide Injection and to continue to drink and void frequently following administration to reduce radiation exposure, particularly during the first hour after administration [see Warnings and Precautions (5.2) ] . 2.4 Image Acquisition Position the patient supine with arms above the head. Begin PET scanning 50 to 100 minutes after the intravenous administration of Gallium Ga 68 Gozetotide Injection. Patients should void immediately prior to image acquisition and that image acquisition should begin at the proximal 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. 2.5 Image Interpretation Gallium Ga 68 Gozetotide binds to prostate-specific membrane antigen (PSMA). Based on the intensity of the signals, PET images obtained using Gallium Ga 68 Gozetotide Injection indicate the presence of PSMA in tissues. Lesions should be considered suspicious if uptake is greater than physiologic uptake in that tissue or greater than adjacent background if no physiologic uptake is expected. Tumors that do not bear PSMA will not be visualized. Increased uptake in tumors is not specific for prostate cancer [see Warnings and Precautions (5.1) ] . 2.6 Radiation Dosimetry Estimated radiation absorbed doses per injected activity for organs and tissues of adult male patients following an intravenous bolus of Gallium Ga 68 Gozetotide Injection are shown in Table 1. The effective radiation dose resulting from the administration of 259 MBq (7 mCi) is about 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. If CT or a transmission source are used for attenuation correction, the radiation dose will increase by an amount that varies by technique. Table 1: Estimated Radiation Absorbed Dose per Injected Activity in Selected Organs and Tissues of Adults after Intravenous Administration of Gallium Ga 68 Gozetotide Injection Organ Absorbed dose (mGy/MBq) Mean SD Adrenals 0.0156 0.0014 Brain 0.0104 0.0011 Breasts 0.0103 0.0011 Gallbladder 0.0157 0.0012 Lower Colon 0.0134 0.0009 Small Intestine 0.0140 0.0020 Stomach 0.0129 0.0008 Heart 0.0120 0.0009 Kidneys 0.3714 0.0922 Liver 0.0409 0.0076 Lungs 0.0111 0.0007 Muscle 0.0103 0.0003 Pancreas 0.0147 0.0009 Red Marrow 0.0114 0.0016 Skin 0.0091 0.0003 Spleen 0.0650 0.0180 Testes 0.0111 0.0006 Thymus 0.0105 0.0006 Thyroid 0.0104 0.0006 Urinary Bladder 0.0982 0.0286 Total Body 0.0143 0.0013 Effective Dose (mSv/MBq) 0.0169 0.0015

None None ( 4 )

The most commonly reported adverse reactions include nausea, diarrhea, and dizziness. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact UCLA Nuclear Medicine at 1-844-963-1855 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of Gallium Ga 68 Gozetotide Injection was evaluated in 960 patients, each receiving one dose of Gallium Ga 68 Gozetotide Injection. The average injected activity was 188.7 ± 40.7 MBq (5.1 ± 1.1 mCi). The most commonly reported adverse reactions were nausea, diarrhea, and dizziness, occurring at a rate of < 1%.

Androgen deprivation therapy and other therapies targeting the androgen pathway Androgen deprivation therapy (ADT) and other therapies targeting the androgen pathway, such as androgen receptor antagonists, can result in changes in uptake of gallium Ga 68 gozetotide in prostate cancer. The effect of these therapies on performance of gallium Ga 68 gozetotide PET has not been established.

Storage and Handling Store Gallium Ga 68 Gozetotide Injection upright in a lead shielded container at 25°C (77°F); excursions are permitted from 15°C to 30°C (59°F to 86°F). Store Gallium Ga 68 Gozetotide Injection within the original container in radiation shielding. Receipt, transfer, handling, possession, or use of this product is subject to the radioactive material regulations and licensing requirements of the U.S. Nuclear Regulatory Commission, Agreement States, or Licensing States as appropriate.