Gallium Ga-68 PSMA-11

1 INDICATIONS AND USAGE Gallium Ga 68 gozeotide 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 )

2 DOSAGE AND ADMINISTRATION 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 up …

3 DOSAGE FORMS AND STRENGTHS Injection: supplied as a clear, colorless solution in a multiple-dose vial containing 18.5 MBq/mL to 185 MBq/mL (0.5 mCi/mL to 5 mCi/mL) of gallium Ga 68 gozetotide in approximately 12 mL at calibration time. Injection: clear, colorless solution in a multiple-dose vial containing 18.5 MBq/mL to 185 MBq/mL (0.5 mCi/mL to 5 mCi/mL) gallium Ga 68 gozetotide in approximately 12 mL at calibration time ( 3 )

4 CONTRAINDICATIONS None None ( 4 )

6 ADVERSE REACTIONS The most commonly reported adverse reactions include nausea, diarrhea, and dizziness. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact UCSF Nuclear Medicine at 1-888-919-0740 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%

7 DRUG INTERACTIONS 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.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary Gallium Ga 68 Gozetotide Injection is not indicated for use in females. There are no available data with Gallium Ga 68 Gozetotide Injection use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. All radiopharmaceuticals, including Gallium Ga 68 Gozetotide Injection, have the potential to cause fetal harm depending on the fetal stage of development and the magnitude of the radiation dose. Animal reproduction studies have not been conducted with gallium Ga 68 gozetotide. 8.2 Lactation Risk Summary Gallium Ga 68 Gozetotide Injection is not indicated for use in females. There are no data on the presence of gallium Ga 68 gozetotide in human milk, the effect on the breastfed infant, or the effect on milk production. 8.4 Pediatric Use The safety and effectiveness of Gallium Ga 68 Gozetotide Injection have not been established in pediatric patients. 8.5 Geriatric Use The efficacy of Gallium Ga 68 Gozetotide Injection in geriatric patients with prostate cancer is based on data from two prospective studies [see Clinical Studies (14) ] . Of the total number of subjects in these studies of Gallium Ga 68 Gozetotide Injection, 691 of 960 (72%) were 65 years of age and older (72%), While 195 (20%) were 75 years of age and older. The efficacy and safety profiles of Gallium Ga 68 Gozetotide Injection appear similar in younger adult and geriatric patients with prostate cancer, although the number of younger adult patients in the trials was not large enough to allow definitive comparison.

12.1 Mechanism of Action Gallium Ga 68 gozetotode binds to prostate-specific membrane antigen (PSMA). It binds to cells that express PSMA, including malignant prostate cancer cells, which usually overexpress PSMA. Gallium-68 (Ga 68) is a β+ emitting radionuclide that allows positron emission tomography (PET).

11 DESCRIPTION 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

10 OVERDOSAGE In the event of an overdose of gallium Ga 68 gozetotide injection, reduce the radiation absorbed dose to the patient where possible by increasing the elimination of the drug from the body using hydration and frequent bladder voiding. A diuretic might also be considered. If possible, an estimate of the radiation effective dose given to the patient should be made.

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied Gallium Ga 68 Gozetotide Injection (NDC 24275-0525-1) is a clear, colorless solution, supplied in a capped glass vial containing 18.5 MBq/mL to 185 MBq/mL (0.5 mCi/mL to 5 mCi/mL) of gallium Ga 68 gozetotide at end of synthesis, in approximately 11 mL. The contents of each vial are sterile, pyrogen-free and preservative-free. The expiration date and time are provided on the container label. Use Gallium Ga 68 Gozetotide Injection within 4 hours of calibration time. Storage and Handling Storage 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. Handling 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.