Establishing the cyclotron and the PET/CT unit in the Republic of Macedonia our experience

Transcription

1 Establishing the cyclotron and the PET/CT unit in the Republic of Macedonia our experience PhD. Marina Zdraveska Kochovska PHI UI for Positron emission tomography, Republic of Macedonia, Skopje

2 Outline Presentation of the Public Health Institution - University Institution for Positron Emission Tomography in the Republic of Macedonia Issues on QA in cyclotron production: Target yield Ion source efficiency Beam transmission Enriched water usage Vacuum level Current situation and future perspectives July 2018, Ohrid, Macedonia

3 Introduction In 2015 officially was marked the beginning of the new era for medical world in the Republic of Macedonia. The cyclotron unit became operational and enabled the installation and operation of the first public PET/CT scanner. It was the biggest advanced technology investment that has ever happened in the field of medical imaging, installation of the cyclotron unit and diagnostic unit with PET/CT. The investment was done by the government of the Republic of Macedonia and the project realized with IAEA July, 2018 Ohrid, Macedonia

4 By installing the first cyclotron in the region the production of short lived radioisotopes become reality. The new developed institution is recognized as Public health institution, University institution and fully covers the own needs, also have a capacity to cover two private PET/CT units in the Republic of Macedonia and wider Balkan area July, 2018 Ohrid, Macedonia

5 Macedonia in Europe and Balkans Macedonia 2 millions inhabitants, encompasses about m2 Skopje the capital 1 million inhabitants Cyclotron July, 2018 Ohrid, Macedonia

6 The current status in the Balkan region Albania no PET/CT (in process of installation), no cyclotron (2.8 millions) Serbia 2 PET/CT no cyclotron (7 millions population) Macedonia 1 cyclotron and 3 PET/CT (2 private and 1 public)(2 millions) Monte Negro ( population)- no PET/CT, no cyclotron Kosovo 1 PET/CT Bulgaria (7 millions)- Varna cyclotron, Sofia hospital cyclotron and PET/CT 3 Croatia one private cyclotron, July, 2018 Ohrid, Macedonia

7 The current status of Nuclear medicine in the Republic of Macedonia 2 Public centers of conventional Nuclear medicine and 1 private PET/CT (3) 1 public and 2 in private hospital 2 SPECT/CT 2 double head SPECT July, 2018 Ohrid, Macedonia

8 The beginnings.. The idea for PET/CT and cyclotron unit dated since 2003 y Start of the project with IAEA 2011 First stone was put Building was finished Start with tests of equipment First production First patient June 2017 (until now almost 1000 patients performed for one year July, 2018 Ohrid, Macedonia

9 The main features. Total area of 2058 m 2 within building and 500 m 2 for production area where radiopharmaceuticals are manufactured, prepared and controlled for their quality. A GE PET trace 860 cyclotron for the production of medical radioisotopes 16,5 MeV (8) Hot cells, (4) modules for synthesis of FDG, (1)for 11C, (1) 68Ga and (1) for NH4 Two CLIO sterile dispensers for the final product in multi dose vials and syringes Two (2) fully equipped QC laboratories for radiopharmaceuticals where it will be certified whether the specifications of the final pharmaceutical product meet the requirements of the European Pharmacopoeia July, 2018 Ohrid, Macedonia

10 The main features. Continuous power supply 160 kva UPS support with automatic startup of relative power generators BMS systems that has been developed for the institution which enable continuous control of the temperature, humidity, and pressures in the production area Access control system for the entirety of the facilities which are guarded by full-time security personnel on a 24-hour basis July, 2018 Ohrid, Macedonia

11 Staffing at the PHI UI for PET Centre 2 physicians (one specialist in nuclear medicine, one specialist in radiology) 1 chemist 4 radio pharmacists (4 MSc) 3 medical physicist (1 PhD, 1 MSc, 1 resident) 7 technologists 2 nurses, Administration staff July, 2018 Ohrid, Macedonia

12 The PET Center being built July, 2018 Ohrid, Macedonia

13 JZU UI PET July, 2018 Ohrid, Macedonia

14 Design structure of the object Cyclotron vault Medical technical gases July, 2018 Ohrid, Macedonia

15 1.CYCLOTRON UNIT July, 2018 Ohrid, Macedonia

16 From the installation of Cyclotron W=20 t

17 Inside the cyclotron vault For the ease of future decommissioning of the facility the rendering of entire internal shielding wall with a layer of concrete brick is suggested.

18 Cyclotron QA Cyclotrons like other radiological equipment all criteria and requirements as regards QA apply The needs for acceptance testing and routine quality control: To verify accomplishment of contractual agreements To characterize performance of the system To optimize use and reduce down time To safeguard the investment.

19 From daily routine 05:00 start environmental and operational tests 05:10 Pre irradiation of 18F target with H2O16 05:2o Activity bolus delivered to a research hot cell, test of production, rinse and drying the line 05:25 start of first 18F production 05:15 Start testing and loading the FDG module and preparing the vials and syringes 06:00 Start preparation of QC equipment 06:20 end of bombardment and delivery of activity to the FDG module 06:25 Drying the target and start with F18-FDG synthesis 08:20 18F-FDG QC completed 08:30 First patient dose dispensed

20 Environmental condition P = -40 kpa; T = 20 C; H = 40 %; W = 20 t; 20 t - Motion detector, - SOP for entrance/exit, - Ventilation system, - Safety system with interlock 120cm

21 Inside the cyclotron - regular maintenance 1 GE Positron Systems (GE Cyclotron PET Trace 860) (16,5 MeV H - ; 8,4 MeV D - ) 4 targets for production of F-18 (x2), N-13, C-11 Check of collimators, carousels,

22 - Technical room - Risk of external irradiation and contamination during regular maintenance

23 Cyclotron operators room

24 Routine QA tests Test of target yield with H 16 2 O Real time checks of irradiation parameters Ion source efficiency Beam transmission Mass of enriched water used Delivery time of radioactive bolus Vacuum levels

25 Check of the yield in 18F - production - irradiation time 60 min - beam current µa -Saturation yield is a measure of the performance of the target Target 4: 2640 mci in 60 min; 38 µa, S = 225,7mCi/µA Target 1: 2626 mci in 60 min; 38 µa, S = 224,8 mci/µa

26 Constancy check of 18F - target using H 2 16 O - As a routine check short pre-irradiation (10 min, 10 µa) on H 2 16 O,delivered to an activity calibrator of a different hot cell. Ratio(Yield with H 2 18 O /Yield with H 2 16 O ) ~ 7,19 Acceptable values of yield with H 2 16 O > 27 mci/µa

27 Check of stability of parameters during irradiation

28 Check of stability of parameters during irradiation Time after SOB 5 min 15 min 25 min 33 min Lower collimator 3,6 ma 3,4 ma 4,1 ma 2,7 ma Upper collimator 2,9 ma 3,4 ma 3,6 ma 3,7 ma Target current 30,2 ma 49,6 ma 50,1 ma 49,8 ma Foil current 46,7 ma 57,2 ma 57,6 ma 56,5 ma Arc current 139,0 ma 158,0 ma 160 ma 159 ma Target pressure 436,5 psi 437,9 psi 437,5 psi 437,9 psi He cooling press. 53,5 psi 55,5 psi 55,0 psi 52,0 psi Ipsmc 430,9 A 430,9 A 431,0 A 431,0 A Beam wide 10,8 % 6,9 % 7,7 % 6,4 % Asymmetry 19,4 % 0,0 % 12,2 % -37,0 % Balance of the current 10,0 ma 0,8 ma -0,2 ma 0,3 ma Efficiency of the Ion source 0,22 % o 0,31 % o 0,31 % o 0,31 % o

29 Efficiency of the ion source Efficiency of the IS is defined as: Target current(µa)/ Arc current (ma) IS produces the beam thanks to a discharge in a flow of neutral H 2 gas During operation at a given value of current on the target should correspond a stable value of arc current in IS A variation in a reference values may be a symptoms of a fault or malfunction Typical values of IS efficiency depends on the type of the system A reference values should be established for each cyclotron just after installation Stability of the efficiency with time can then be checked as a part of routine QA For PET trace typical value of IS are >0,20% (0,31%)

30 Check of the mass of H 2 18 O water loaded For 18F targets verification of target loading system (syringe pumps, valves, fittings) are in good order and tighten is very important, Periodically check of the weight of a bolus water by filling the target and delivery the contents in a clean vial is recommended It is recommended to note the initial weight of syringes or vials of enriched water in use and measure the residual mass at the time of refilling. Dividing by the number of filling operations it is possible to estimate the average mass loaded, this should be in agreement with typical reference values.

31 Stability of vacuum levels Record of vacuum level on daily basis, helps to prevent and pay attention if there are eventual faults in the vacuum system.

32 Classified production laboratory for FDG Protective gloves CLIO system for dispensing In vials and syringes with minimal manual application Hand manipulators

33 Classified production laboratory for 11 C, 68 Ga

34 Laboratory for therapy Ventilation system who prevents leakage of radioactive material and contamination Automatic interlock for guarantee that certain components will be approved only if some manual, mechanical, electrical conditions are fulfilled During delivery of radioactive material it is impossible to open the hot cells.

35 18F-FDG Injection QC Pre-Release Testing Membrane filter integrity: Bubble point > 3,45 bari (50psi) Radionuclide Identity: T1/2 determination ( min) ph = 4,5-7,5 Radiochemical Purity:>95% and Identity Analysis TLC: Silica gel, Solvent: Acetonitrile: Water (95:5) Residual Solvents: Gas Chromatography Acetonitrile: < 0,04%/V(0,41 mg/ml) Ethanol: < 0,5/V (1-5 mg/ml) Chemical purity: Kryptofix 222 Analysis: <50 µg/ml Bacterial endotoxin test <175units/V Post release test: Sterility testing and radionuclide purity.

36 Quality Control laboratory 1 GC Dose calibrator for check of T1/2

37 Quality Control laboratory 2 Gamma spectrometry

38 Environmental monitoring system for gases and liquid waste

39 Future plans 11C production and use of 11C Cholline Introduce of other 11C radiopharmaceuticals (methionine, acetate) Possibility of quantification of radiation dose in target radiotherapy Installation of solid or liquid target for 64Cu 68Ga - DOTA

40 2. DIAGNOSTIC PART

41 Diagnostic part first floor

42 Equipment in diagnostic part PET/CT system (Siemens Biograph mct) Dose calibrator Survey meters, Hand and foot monitoring, Performed 1000 patients (June July 2018) The plan for next year is patients.

43 Diagnostic part PET/CT Siemens Biograph mct

44 Siemens Biograph mct Straton X tube fast gantry rotation time 0,30 s and high temporal resolution in 150ms; 3 rings, LSO crystal with fast scintillation decay time of 40ns and the highest density available;

45 (6) Injection rooms WIS automatic injector

46 Dose calibrator Capintec Hand and foot monitor

47 Radiation protection and monitoring equipment Lead L block Dose calibrator Finger dosemeters Personal dosemeters Lead shielding TLD

48 Personal protection equipment

49

50 Conclusion On site cyclotron gives great opportunity for producing diagnostic as well as therapeutic radionuclide's At the moment training of qualified and skilled professionals is a fundamental and very important task.

51 Thank you for your attention!