Illuccix Dosage

Radiation Safety - Drug Handling

After reconstitution and radiolabeling of ILLUCCIX, the vial contains Gallium Ga 68 Gozetotide Injection. 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.

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. Only use solutions that are clear, colorless or at most slightly yellow, and without visible particles.
• Gallium Ga 68 Gozetotide Injection may be diluted with sterile 0.9% Sodium Chloride Injection, USP.
• Assay the final dose in a dose calibrator immediately before administration to the patient.
• 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.

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)].

Drug Preparation

ILLUCCIX is supplied as a 3-vial kit in two different configurations [see Dosage Forms and Strengths (3)] for preparation of Gallium Ga 68 Gozetotide Injection with eluate from one of the following (see below for specific instructions for use with each Ga 68 source):

• Cyclotron produced via GE FASTlab TM (Configuration A)
• Eckert & Ziegler (EZAG) GalliaPharm ® Germanium 68/Gallium 68 (Ge 68/Ga 68) generator (Configuration A)
• IRE Galli Eo ® Ge 68/Ga 68 generator (Configuration B)

The Ge 68/Ga 68 generators and cyclotron are not supplied with ILLUCCIX.

Components of ILLUCCIX include:

• Vial 1 (Gozetotide Vial) contains 25 mcg of gozetotide and 10 mcg of D-mannose (stabilizer) as a lyophilized powder.

• Vial 2 (Acetate Buffer Vial) contains 150 mg anhydrous sodium acetate in HCl buffer.
• Vial 3 (Sterile Vacuumed Reaction Vial) is a sterile, evacuated vial that serves as the collection vial for Ga 68 chloride and radiolabeling reaction.

Prepare Gallium Ga 68 Gozetotide Injection for intravenous injection according to the following aseptic procedure:

1. Use suitable shielding to reduce radiation exposure.
2. Wear waterproof gloves.
3. If Ga 68 is generator produced, test the Ga 68 chloride eluate for Ge 68 breakthrough weekly by a suitable method according to manufacturer recommendations. Ge 68 breakthrough and other gamma emitting radionuclides should meet the specifications (≤0.001%) provided by the manufacturer. If Ga 68 is cyclotron produced, test for Ga 66 and Ga 67 (with specification of ≤2% combined total) when a new Zn 68 is introduced for manufacturing.
4. Place a “radioactive” label on Vial 3 (Sterile Vacuumed Reaction Vial) with product name, lot number, and date.
5. Remove the vial cap from Vial 1, Vial 2, and Vial 3.
6. Swab the top of each vial with alcohol to disinfect the surface and allow the top of each vial to dry.
7. Note that to minimize any potential metallic contamination, the shortest possible needle should be used for the transfer of the gallium solution from the generator. The needle should be clean and dilute acid resistant.
8. Use only plastic syringes for preparation and administration. Do not use syringes with rubber plungers.
9. Note that prior to use of any vial, confirm the correct vial is being used by a visual check of the vial label.
10. Follow the specific reconstitution procedure below, dependent on Ga 68 source. Then continue with the dilution and radiosynthesis procedure below.

Preparation with Cyclotron Produced Ga 68 via GE FASTlab

Collection of Gallium Ga 68 Chloride

1. After purification by the FASTlab, the Ga 68 chloride solution is passed through a sterile filter and into the cassette product vial automatically by the FASTlab.
2. Pierce Vial 3 (Sterile Vacuumed Reaction Vial) with a sterile needle connected to a 0.2 micron sterile vented filter (not supplied) to maintain atmospheric pressure within the vial during the reconstitution process.
3. Aseptically transfer 5 mL of Ga 68 chloride solution into Vial 3.

Reconstitution and Radiolabeling Reaction Procedure

1. Insert a sterile 10 mL syringe with a needle into Vial 2 (Acetate Buffer Vial Configuration A) and draw up the contents of the vial (2.5 mL).
2. Inject the contents of the 10 mL syringe into Vial 1 (Gozetotide Vial).
3. Gently swirl Vial 1 to ensure the product is thoroughly dissolved.
4. Insert a sterile 10 mL syringe with a needle into Vial 1 containing the dissolved gozetotide and draw up the contents of the vial.
5. Transfer the contents of the 10 mL syringe to the reaction Vial 3 containing the Ga 68 chloride.
6. Wait for 5 minutes for radiolabeling to take place at ambient temperature (25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F)).
7. Assay the whole vial containing the Gallium Ga 68 Gozetotide Injection for total radioactivity using a dose calibrator, calculate the radioactivity concentration and record the result.
8. Perform the quality control of Gallium Ga 68 Gozetotide Injection according to the recommended methods in the Subsection 2.5 Specifications and Quality Control.
9. Prior to use, visually inspect the solution behind a shielded screen for radioprotection purposes. Only use solutions that are clear without visible particles.
10. Keep the vial containing the Gallium Ga 68 Gozetotide Injection upright in a radio-protective shield container at ambient temperature until use.
11. After reconstitution and addition of Ga 68 chloride to the kit components in the reaction Vial 3, use Gallium Ga 68 Gozetotide Injection within 4 hours. The final volume of the Gallium Ga 68 Gozetotide Injection is 7.5 mL.

Preparation with Eckert & Ziegler GalliaPharm Generator

Collection of Gallium Ga 68 Chloride

1. Prepare a syringe containing 5 mL of sterile ultrapure 0.1 M HCl provided with the GalliaPharm Generator for elution.
2. Pierce Vial 3 (Sterile Vacuumed Reaction Vial) with a sterile needle connected to a 0.2 micron sterile vented filter (not supplied) to maintain atmospheric pressure within the vial during the reconstitution process.
3. Connect the male luer of the outlet line of the GalliaPharm generator to a sterile needle.
4. Connect Vial 3 directly to the outlet line of the GalliaPharm generator by pushing the needle through the rubber septum and place the vial in a radiation shielded container.
5. Elute the generator directly with the 5 mL 0.1 M HCl from step 1 into Vial 3 according to the instructions for use of the GalliaPharm generator that are supplied by Eckert & Ziegler. Perform the elution manually or by means of a pump. Collect 5 mL of eluate.
6. At the end of the elution, disconnect the generator from Vial 3 by removing the needle from the rubber septum.

Reconstitution and Radiolabeling Reaction Procedure

1. Insert a sterile 10 mL syringe with a needle into Vial 2 (Acetate Buffer Vial Configuration A) and draw up the contents of the vial (2.5 mL).
2. Inject the contents of the 10 mL syringe into Vial 1 (Gozetotide Vial).
3. Gently swirl Vial 1 to ensure the product is thoroughly dissolved.
4. Insert a sterile 10 mL syringe with a needle into Vial 1 containing the dissolved gozetotide and draw up the contents of the vial.
5. Transfer the contents of the 10 mL syringe to Vial 3 (Sterile Vacuumed Reaction Vial) containing the Ga 68 chloride.
6. Wait for 5 minutes for radiolabeling to take place at ambient temperature (25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F)).
7. Assay the whole vial containing the Gallium Ga 68 Gozetotide Injection for total radioactivity using a dose calibrator, calculate the radioactivity concentration and record the result.
8. Perform the quality control of Gallium Ga 68 Gozetotide Injection according to the recommended methods in the Subsection 2.5 Specifications and Quality Control.
9. Prior to use, visually inspect the solution behind a shielded screen for radioprotection purposes. Only use solutions that are clear without visible particles.
10. Keep the vial containing the Gallium Ga 68 Gozetotide Injection upright in a radio-protective shield container at ambient temperature until use.
11. After reconstitution and addition of Ga 68 chloride to the kit components in the reaction Vial 3, use Gallium Ga 68 Gozetotide Injection within 4 hours. The final volume of the Gallium Ga 68 Gozetotide Injection is 7.5 mL.

Preparation with IRE Galli Eo Generator

Collection of Gallium Ga 68 Chloride

1. Connect the male luer of the outlet line of the Galli Eo generator to a sterile needle.
2. Elute the generator directly into Vial 3 (Sterile Vacuumed Reaction Vial) according to the instructions for use of the Galli Eo generator that are supplied by IRE. Collect 1.1 mL of eluate.
3. At the end of the elution, disconnect the generator from Vial 3 by removing the needle from the rubber septum.

Reconstitution and Radiolabeling Reaction Procedure

1. Insert a sterile 10 mL syringe with a needle into Vial 2 (Acetate Buffer Vial Configuration B) and draw up the contents of the vial.
2. Inject the contents of the 10 mL syringe into Vial 1 (Gozetotide Vial).
3. Gently swirl Vial 1 to ensure the product is thoroughly dissolved.
4. Insert a sterile 10 mL syringe with a needle into Vial 1 containing the dissolved gozetotide and draw up the contents of the vial (6.4 mL).
5. Transfer the contents of the 10 mL syringe to the reaction Vial 3 containing the Ga 68 chloride.
6. Wait for 5 minutes for radiolabeling to take place at ambient temperature (25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F)).
7. Assay the whole vial containing the Gallium Ga 68 Gozetotide Injection for total radioactivity using a dose calibrator, calculate the radioactivity concentration and record the result.
8. Perform the quality control of Gallium Ga 68 Gozetotide Injection according to the recommended methods in the Subsection 2.5 Specifications and Quality Control.
9. Prior to use, visually inspect the solution behind a shielded screen for radioprotection purposes. Only use solutions that are clear without visible particles.
10. Keep the vial containing the Gallium Ga 68 Gozetotide Injection upright in a radio-protective shield container at ambient temperature until use.
11. After reconstitution and addition of Ga 68 chloride to the kit components in the reaction Vial 3, use Gallium Ga 68 Gozetotide Injection within 4 hours. The final volume of the Gallium Ga 68 Gozetotide Injection is 7.5 mL.

Flow diagrams are provided for the radiosynthetic process to be followed at the radiopharmacy site for:

• ILLUCCIX Configuration “A” when using Ga 68 prepared by cyclotron ( Figure 1) or
• ILLUCCIX Configurations “A” or “B” when using an indicated GMP-grade EZAG GalliaPharm Ge 68/Ga 68 Generator ( Figure 2) or IRE Galli Eo Ge 68/Ga 68 Generator ( Figure 3).

Figure 1: Preparation with Cyclotron Produced Ga 68 via GE FASTlab

Note: Ga 68 from GE FASTlab is aseptically transferred into the Sterile Vacuumed Reaction Vial.

Use “Configuration A” with cyclotron produced Ga 68 via GE FASTlab [see How Supplied/Storage and Handling (16)].

Figure 2: Preparation with Eckert & Ziegler GalliaPharm Generator

Note: Use “Configuration A” with EZAG GalliaPharm Ge 68/Ga 68 generator [see How Supplied/Storage and Handling (16)].

Figure 3: Preparation with IRE Galli Eo Generator

Note: Use “Configuration B” with IRE Galli Eo Ge 68/Ga 68 generator [see How Supplied/Storage and Handling (16)].

Specifications and Quality Control

Perform the quality controls in Table 1 behind a lead glass shield for radioprotection purposes.

Table 1: Specifications for the Radiolabeled Imaging Product (Gallium Ga 68 Gozetotide Injection)

Perform one of the following:

Cutting Technique

1. Pour ammonium acetate 1 M/methanol (1/1 V/V) solution to a depth of 3 mm to 4 mm in the developing chamber, cover the chamber and allow it to equilibrate.
2. Draw a pencil line at 1 cm from the bottom of the iTLC strip, and a dotted line 5 cm from the pencil line. Apply a drop of gallium Ga 68 gozetotide at the center of the pencil line.
3. Place the iTLC strip in the developing chamber and allow it to develop for a distance of 10 cm from the point of application.

1. Cut the iTLC strip following the dotted line and measure each piece with the radioactivity dose calibrator.
2. Calculate the quantity (in percent) of gallium Ga 68 gozetotide in the solution using the formula:

% Gallium Ga 68 gozetotide=(Activity top piece)/(Activity bottom piece+Activity top piece) ×100

Scanning Technique

1. Pour ammonium acetate 1 M/methanol (1/1 V/V) solution to a depth of 3 mm to 4 mm in the developing chamber, cover the chamber and allow it to equilibrate.
2. Draw a pencil line at 1 cm from the bottom of the iTLC strip and apply a drop of gallium Ga 68 gozetotide at the center of the pencil line.
3. Place the iTLC strip in the developing chamber and allow it to develop for a distance of 10 cm from the point of application.
4. Scan the iTLC with a radiometric iTLC scanner.

1. Calculate the quantity (in percent) of gallium Ga 68 gozetotide in the solution by integration of the peaks on the chromatogram.
2. The retention factor (Rf) specifications are:

Free and colloidal Ga 68 species, Rf = 0 to 0.1,

Gallium Ga 68 gozetotide, Rf = 0.6 to 1.

Image Acquisition

Position the patient supine with arms above the head. 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 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.

Image Interpretation

Gallium Ga 68 gozetotide binds to PSMA. Based on the intensity of the signals, PET images obtained using gallium Ga 68 gozetotide indicate the presence of PSMA in tissues.

Imaging Prior to Initial Definitive or Suspected Recurrence Therapy

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 express PSMA will not be visualized. Increased uptake in tumors is not specific for prostate cancer [ see Warnings and Precautions ( 5.1) ].

Imaging to Select Patients for Lutetium Lu 177 Vipivotide Tetraxetan Therapy

​For patient selection, interpret ILLUCCIX PET in conjunction with patients’ clinical history and imaging from other modalities, including diagnostic anatomical imaging in clinically relevant regions, such as chest, abdomen, and pelvis. On ILLUCCIX PET images, compare uptake of gallium Ga 68 gozetotide at sites of suspected prostate cancer (lesions) with uptake in normal liver. Lesions should be considered positive if gallium Ga 68 gozetotide uptake is greater than normal liver and negative if gallium Ga 68 gozetotide uptake is less than or equal to normal liver.

​Patients should be considered eligible for lutetium Lu 177 vipivotide tetraxetan therapy if at least one tumor lesion is positive and all lesions on anatomical imaging larger in short axis than size criteria are also positive [size criteria: organs ≥ 1 cm, lymph nodes ≥ 2.5 cm, bones (soft tissue component) ≥ 1 cm]. Patients should be considered ineligible for lutetium Lu 177 vipivotide tetraxetan therapy if all lesions are negative or any one lesion larger than size criteria is negative.

​The interpretation of ILLUCCIX PET may differ depending on imaging readers [ see Warnings and Precautions ( 5.1) ].

​

For therapeutic information, refer to the prescribing information of lutetium Lu 177 vipivotide tetraxetan.

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 2.

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 2: Estimated Radiation Absorbed Dose per Injected Activity in Selected Organs and Tissues of Adults after Intravenous Administration of Gallium Ga 68 Gozetotide Injection