International Workshop PSD-11 Delft. Clive Naidoo (PhD Chemistry) Dept Head: Radionuclide Production ithemba LABS South Africa

Transcription

1 International Workshop PSD-11 Delft Clive Naidoo (PhD Chemistry) Dept Head: Radionuclide Production ithemba LABS South Africa

2 ithemba LABS Structure Directorate HR, Finance & General Admin Electronic and Information Services Radionuclide Prod Research Radiation Therapy Accelerator Infrastructure Technical Support & Site Services

3 RPD OBJECTIVES To produce radiopharmaceuticals for the benefit of the South African Nuclear Medicine community. To produce longer-lived radionuclides for the export market. Research & Development and Training Program.

4 ithemba LABS Layout Polarized ion source Separated-Sector Cyclotron Facility SSC Target vaults Spectrometer SPC2 ECR ion source SPC1 electronics electronics Radioisotope production Proton therapy Neutron therapy beam swinger m

5 Separated Sector Cyclotron (200 MeV)

6 RPD beam time allocation Monday night 17h00 to 7h00 (14 h) Tuesday night 17h00 to 7h00 (14 h) Wednesday night 17h00 to 7h00 (14 h) Thursday night 17h00 to 5h00 (12 h) On average 54 h / week (32%)

7 RPD beam time allocation with beam splitter

8 ithemba LABS Products produced under cgmp principles Radionuclide Half-Life (hours) 18 F 1.83 Nuclear Reaction 15 O(p,n) 18 F 67 Ga 78.3 Zn(p,xn) 67 Ga Ge(p,x) 67 Ga 81 Rb/ 81m Kr 4.58 Kr(p,xn) 81 Rb 123 I I(p,5n) 123 Xe 123 I 68 Ge/ 68 Ga generator 68 Ge = 271 d 68 Ga = 68 min 69 Ga(p,2n) 68 Ge Radiopharmaceutical Main Use Product 18 F-FDG Glucose metabolic studies 67 Ga-citrate Localization of certain tumours and inflammatory regions 81 Rb/ 81m Kr generator Lung ventilation studies 123 I-sodium iodide Thyroid studies 123 I-mIBG Localization of certain tumours such as neuroblastoma, pheochromocytoma 68 Ga DOTA-peptides Typically detection of neuroendocrine tumours

9 ithemba LABS other products Radionuclide Half-Life Nuclear Reaction Main Use (days/years) 82 Sr 25 days Rb(p,xn) 82 Sr Used to manufacture 82 Sr/ 82 Rb generators 68 Ge 271 days Ga(p,xn) 68 Ge Used to manufacture 68 Ge/ 68 Ga generators and calibration sources for PET CT scanners 88 Y days Sr(p,xn) 88 Y Non medical application calibration sources 109 Cd 453 days Ag(p,xn) 109 Cd Non-medical application-calibration sources 22 Na & Na positron sources years Mg(p,n) 22 Na Used in Material Sciences -Positron Annihilation Studies

10 Horizontal Beam Target Station (HBTS) Produce: 67 Ga, 123 I, 81 Rb, 68 Ge, 82 Sr, 22 Na, 88 Y, 57 Co and 109 Cd HBTS Target and target holders 66 MeV proton beam with an intensity of ~90 µa

11 Vertical Beam Target Station (VBTS) Produce in Tandem 82 Sr/ 68 Ge and 22 Na/ 68 Ge VBTS Thick Target Holders 66 MeV proton beam with an intensity of ~250 µa VBTS Tandem targets VBTS Tandem targets

12 18 F- Bombardment Station 18 F Target Station (66 MeV to 18 MeV) Target Control System Enriched water target

13 Beam Splitter

14 RPD Control Room Automated Transport System Control systems such as cooling systems (water and helium), interlocking systems and transport system

15 Chemical Processing Facilities 18 F-Automated Chemical Processing Hot Cells Manual Manipulator Hot Cells (two banks of 7)

16 3 Independent clean rooms 68 Ge/ 68 Ga 18 F-FDG 123 I / 67 Ga

17 Dispensing facilitiesnts Comecer Hotcells & Timothea Dispensing Facilities

18 Quality Control Facilities GC HPLC Capintec Ionisation Chamber

19 Quality Control Microlab Sterility and endotoxin testing

20 QC Raw material

21 Packing and Dispatch As per IATA Regulations

22 Tandem target for the production of 22 Na and 68 Ge 66 MeV protons 20 mm MeV MeV MeV MeV Mg material: 99.99% (15 g) MeV MeV MeV MeV MeV

23 Chemical Processing A magnesium target (ca 15 g, 12 mm thick, 20 mm diameter) is bombarded for several weeks with a 66 MeV proton beam at a beam current of 80 μa (in the higher energy window MeV). [Generally production rate is 1 mci / h). The target is dissolved in 3.0 M citric acid and then adjusted to obtain a 0.2 M citric acid M TEA - 80% methanol solution. The solution is pumped through a column containing 10 g of the macroporous cation exchanger AG MP 50. Washing solutions: 0.2 M citric acid M TEA - 80% methanol, followed by 0.1 M EDTA M TEA. The resin is then converted to the ammonium form with 1.0 M ammonia 80% methanol and 22 Na is eluted with 1.0 M ammonium carbonate (100 ml) passing through 10 g of the chelating resin Chelex 100 (in the ammonium form) to remove the last traces of magnesium and other elements. The eluate is heated in a conical titanium vessel to evaporate the ammonia and water. 22 Na is obtained as the carbonate salt in a small volume. All reagents are purified to remove sodium prior to the ion exchange separation Final Specification: >800 Ci 22 Na / g

24 22 Na Chemical Processing hot cell panel

25 Capsule Dispensing The specified amount of 22 Na carbonate solution is dispensed from the bulk vial and placed in a V-vial and evaporated to about µl. Final activity check is done with the Capintec Ionisation Chamber. The rear part of the capsule is clamped in a holder with the post facing upwards and level. The 22 Na is then transferred, in 10 μl volumes, into the tantalum cup with a semi-automated dispensing apparatus. This is evaporated to incipient dryness, before the next volume is dispensed. When all the activity of 22 Na has been transferred into the cup, the front part of the capsule is loosely screwed onto the rear part. The capsule is finally sealed to a defined torque value (20 Nm) using a special holder to clamp the capsule tightly. The external surface of the capsule is washed with methanol and then rinsed with deionised water. The capsule is dried and a smear test is done. The source is then placed under vacuum for 24 h to ensure integrity of the capsule. The washing step is repeated and another smear test is done after the vacuum test. The positron capsule is then packed into a lead pot, the lead pot is sealed and finally packed in a container for shipment to the user.

26 Positron Capsule

27 Dispensing apparatus

28 Holder to seal the capsule

29 Apparatus for vacuum testing

30 HPGe detector for final measurements

31 Na-22 sales and forecasts

32 Production Challenges Limited beam time for the irradiation of Mg targets at ithemba LABS. Alternative company s that could produce 22 Na does not meet ithemba LABS product specification of >800 Ci 22 Na / g for large sources. Alternative company s needed to irradiate the Mg target material and for ithemba LABS to do the chemical processing, not economical viable (cost of irradiation US$ 6000 / mci 22 Na). The production of sources is limited to a maximum of 50 mci for the ease of handling and to minimise radiation exposure to staff. NB: Upon receiving the larger sources from ithemba LABS, just do your smear tests as required by your RPO and install.

33 Thank You For Your Attention