Operating Manual. Stand 01/2015, Version 1.0 Version 1.0 Page 1/12

Transcription

1 Operating Manual Stand 01/2015, Version 1.0 Version 1.0 Page 1/12

2 Content Intended Use... 3 Introduction... 3 Installation of the Cassette... 4 Preparation of the Peptide and PSMA... 7 Labeling Procedure for Peptides/DKFZ-PSMA-11 Checklist... 8 Preparation of the Equipment (Citrate) Labeling Procedure for Citrate Checklist Quality Control for labeled Gallium Functionality Test of Radiolabeling Customer Service Version 1.0 Page 2/12

3 1. Intended Use The itg Ga-68 Cassette and itg Ga-68 Radiolabeling/Citrate KITs are to be used with the iqs Ga-68 Fluidic Labeling Module and the itg Ge-68/Ga-68 Generator only. The itg Ga-68 Radiolabeling KIT has been developed for the fast and convenient synthesis of Ga-68 DOTA-peptides, namely DOTA- NOC, DOTA-TOC and DOTA-TATE as well as of Ga-68 PSMA (DKFZ-PSMA-11). The itg Ga-68 Citrate KIT is used for the synthesis of Ga-68 Citrate. Both, the Ga-68 Cassette and the KITs are designed as one product and should be used together to achieve best results. Using the Cassette or the KITs without the counterpart might have a negative influence on the labeling performance. Furthermore, the filters, syringes, vials and needles required for the synthesis are delivered with the itg Ga-68 Radiolabeling KIT and are not part of the Cassette. The instructions given herein are valid for the synthesis with the itg Ga-68 Cassette together with the KITs (only with the iqs Ga-68 Fluidic Labeling Module and itg Ge-68/Ga-68 Generator). 2. Introduction The itg Ga-68 Cassette and itg Ga-68 Radiolabeling and Citrate KITs were developed to meet the requirements of modern production of radiopharmaceuticals. All chemicals required for the radiolabeling of DOTA-peptides and the synthesis of Citrate are included in the KIT (apart from the peptide). In addition to the chemicals, all accessories such as syringes, needles, vials and filters are integrated in the Radiolabeling KIT. The preassembled fluidic system of the iqs Ga-68 Fluidic Labeling Module are packed sterile in the single use itg Ga-68 Cassette which only has to be clicked into the iqs Ga-68 Fluidic Labeling Module and is then ready to be used. Version 1.0 Page 3/12

4 3. Installation of the Cassette 2 3 Attach SMALL sterile filter from the KIT Figure 1: Assembled fluidic system Attach LARGE sterile filter from the KIT 6 7 1) Elution Pump System 2) line (short capillary) 3) line (long capillary) 4) / Valve 5) / calve 6) Reactor 7) Peptide Pump system After removing the cassette from the blister attach the sterile filters (from Radiolabelling Kit) to the positions marked above as shown in Figure 1. ATTENTION: THE CARTIRIDGE INSTALLED IN THE CASSETTE IS NOT SUITABLE FOR CITRATE LABELING. FOR CITRATE PLEASE ATTACH THE CARTRIDGE DELIVERED WITH THE CITRATE KIT Figure 2: Radiolabeling KIT Accessory kit (2x large sterile filter and 1x air filter, to be attached to the cassette ) 5) chemicals with required syringes and needle vial with needle and ventilation needle vial with sterile filter air filter needle and ventilation needle Version 1.0 Page 4/12

5 1) Place the reactor in the heating 2) Connect the Peptide Pump System to the generator 3) Attach the Peptide Pump System and fix the reactor capillary with the hook and close the fixing bar 4) Attach the Elution Pump System and fix the reactor capillary with the hook and close the fixing bar and fix the cartridge line with the hook 5) Attach the /waste valve. (Make sure that the line is underneath the valve) together with the cartridge. Therefore, push back the cartridge holder. 6) Fix the product line (short capillary) with the fixations to the right opening Version 1.0 Page 5/12

6 7) Fix the waste line (long capillary) with the fixations to the left opening 8) Attach the / valve; fix the capillary with the hook. Make sure all other capillaries are held in position with this valve 9) Install sterile filter* at product outlet (left side) 10) Attach 70 mm needles* to both outlets 11) Attach the ventilation needle* and air filter* to the evacuated vial (No 7)* 12) Attach ventilation needle* to the waste vial (No 6)* Version 1.0 Page 6/12

7 13) Place vials in lead pots, and lead pots on the lift system (product right, waste left) and remove needle covers 14) Lift the lead pots (by pulling the levers). Make sure the needles penetrate properly through the septum 15) Turn the valves to the position shown above. Make sure the knobs of the module are in // position 16) the front doors, then the cover All parts marked with a * are part of the itg Ga-68 Radiolabeling KIT 4. Preparation of the Peptide and PSMA Peptide: 1. Dissolve peptide with 0.25 M NaAc buffer (use 100 µl per 25 µg peptide). 2. Dispense single portion containing 100µl (25 µg peptide). PSMA: 1. Dissolve PSMA with 0.25 M NaAc buffer (use 100 µl per 10 µg peptide). 2. Dispense single portion containing 100 µl (10 µg peptide). Version 1.0 Page 7/12

8 5. Labeling Procedure for Peptides/ PSMA Checklist 1. Make sure that the heating is switched on (set point 105 C) 2. Awaking syringe: 2 ml Awaking solution (Vial A) Connect Awaking syringe to Cartridge port Cartridge Awaking syringe and send 5 times 5 ml air 3. Remove syringe from Cartridge Port and connect to Peptide Port 4. Change the // valve to Change the / valve to 5. Send slowly 5 times 5 ml air with Peptide syringe. Wait minimum of 5 sec between each push 6. Change the // valve to Change the / valve to 7. Remove syringe, fill syringe with 5 ml NaCl and connect syringe to Cartridge port. Cartridge syringe and send 4 times 5 ml air 8. Remove syringe from Cartridge Port and connect to Peptide Port 9. Change the // valve to Change the / valve to 10. Send slowly 5 times 5 ml air with Peptide syringe. Wait minimum of 5 sec between each push 11. Remove syringes and open the cover, check for leakage and close the cover 12. Change the // valve to Change the / valve to 13. Fill syringes: Generator syringe: HCl (Vial G), no air and connect to Generator port Peptide syringe: Buffer (Vial B), add 100 µl peptide/psma, fill up with air and connect to Peptide port Cartridge syringe: 5 ml NaCl, fill up with air and connect to Cartridge port min after heating was switched on Peptide syringe and send 4 times 5 ml air 15. Generator syringe min after the elution of the generator Change the // valve to Change the / valve to 17. Send slowly 5 times 5 ml air with Peptide syringe. Wait minimum of 5 sec between each push Version 1.0 Page 8/12

9 18. Change the // valve to Change the / valve to 19. Cartridge syringe and send 4 times 5 ml air 20. Change the // valve to Change the / valve to 21. Send slowly 5 times 5 ml air with Peptide syringe. Wait minimum of 5 sec between each push Warning: Max. pressure 2 bar! 22. Change valve the / valve to Change the // valve to Change the / valve to 23. Remove the syringe from Cartridge Port. Fill new syringe with Elution Solution (Vial E) and connect to Cartridge Port 24. Cartridge syringe Send 5 times 5 ml air 25. Remove the syringe from Cartridge Port. Fill new syringe with 5 ml Sodium Chloride Solution and connect to Cartridge Port 26. Cartridge syringe. Send 5 times 5 ml air 27. Switch off heating, remove lead pots and cover them with lid. Attach needle covers Version 1.0 Page 9/12

10 6. Preparation of the Equipment (Citrate) ATTENTION: THE CARTIRIDGE INSTALLED IN THE CASSETTE IS NOT SUITABLE FOR CITRATE LABELING. FOR CITRATE PLEASE ATTACH THE CARTRIDGE DELIVERED WITH THE CITRATE KIT 7. Labeling Procedure for Citrate Checklist Cartridge syringe: 2 ml sodium chloride Connect syringe to Port Cartridge Cartridge Syringe and send 4 times 5 ml air Remove syringe from Cartridge Port and connect to Peptide Port Change the // valve to Change the / valve to Send slowly 5 times 5 ml air with Peptide syringe. Wait minimum 5 sec between each push Remove syringes and open the cover, check for leakage and close the cover Change the // valve to Change the / valve to Fill syringes: Generator syringe: HCl (Vial G), no air and connect to Generator port Peptide syringe: Neutralization solution (Vial N), fill up with air connect to Peptide port Cartridge syringe: 0.5 ml NaCl (3 ml syringe), fill up with air connect to Cartridge port Generator syringe Neutralization Peptide syringe slowly within 30 seconds into reactor Send 5 times 5 ml air 1 min after Neutralization Change the // valve to Change the / valve to Send slowly 5 times 5 ml air with Peptide syringe. Wait minimum 5 sec between each push Change the // valve to Change the / valve to Version 1.0 Page 10/12

11 Cartridge syringe and send 4 times 5 ml air Change the // valve to Change the / valve to Send slowly 5 times 5 ml air with Peptide syringe. Wait minimum 5 sec between each push Change valve the / valve to Change the // valve to Change the / valve to Fill syringe with eluent solution (Vial E), fill up with air, connect to Cartridge Port and elute. Send 4 times 5 ml air Cartridge syringe with 3 ml sodium chloride and elute. Send 5 times 5 ml air 8. Quality Control for labeled Gallium For quality control it is recommend to follow the instructions given in the monograph of the European Pharmacopoeia (Monograph N : 2482). 9. Functionality Test of Radiolabeling Citrate: PSMA: DOTA: MeOH/glacial acetic: Mix MeOH and glacial acetic acid in a ratio of 9/1 Run ITLC-SG in this solution Free 68-Ga stays on the bottom; is going to the front MeOH/1 M NH 4 OAc: Solve 3.85 g NH 4 OAc in 50 ml water Mix NH 4 OAc solution with MeOH in a ratio of 1/1 Free 68-Ga stays on the bottom; is going to the front 0.1 M tri sodium citrate buffer: Weigh 1.47 g sodium citrate into a 50 ml container. Add water (app. 25 ml) and 0.5 ml HCl 30 %. Measure the ph. The value should be 4-5. If necessary add more acid. Fill the up to 50 ml with water Free 68-Ga is going with the front, stays on the bottom The yield of the labeled product can be calculated by the ratio of the activity of the product to the sum of activity of the waste and the cartridge. The yield has to be 91 %. Version 1.0 Page 11/12

12 10. Customer Service For further information please contact our customer service. We will be glad to assist you. Customer Service / Sales Phone Fax sales@itg-garching.de ITG Isotope Technologies Garching GmbH Lichtenbergstr Garching (near Munich airport) Germany Version 1.0 Page 12/12