1. ISOL technique for radiopharmaceuticals development
XIV Seminar on Software for Nuclear, Subnuclear and Applied Physics,
Alghero, 8th June 2017
The ISOLPHARM Project
ISOL technique for radiopharmaceuticals development
Michele Ballan
INFN –LNL
Michele Ballan

2. Overview ⚛ Radiopharmaceutical production: current techniques
⚛ The SPES project at LNL
⚛ Radiopharmaceutical production: current techniques
⚛ ISOLPHARM: a new method based on ISOL technique
⚛ Innovative radio-isotopes for nuclear medicine (ISOLPHARM2)
⚛ Experimental activities
⚛ Conclusions
Michele Ballan

3. SPES Facility Layout New infrastructure for: Application Facility
Unico punto in cui si parla di building&infrastr., poi c’è la visita.
E’ stato realizzato l’edificio per il ciclotrone, le stazioni di irraggiamento ISOL e per le aree applicative, il sistema di selezione in massa. Il nuovo edificio è collegato all’edificio ALPI.
The new building has a surface of almost 3600 mq with an underground level connected to the third experimental hall and the ALPI building. The beam transport, together with the CB and the Medium Resolution Mass Separator, will be mounted inside the third exp hall and the RFQ will be inside the ALPI building.
New infrastructure for:
Application Facility
Cyclotron
RIB facility
Michele Ballan

4. SPES: The future of LNL SPES-RIB facility SPES Neutron facility
22/04/2018
SPES is: 1) A second generation ISOL facility (for neutron-rich ion beams)
2) An interdisciplinary research center (for p,n applications)
SPES-DRIVER
SPES-RIB facility
Financed &
Under construction
In commissioning
Cyclotron installation & commissioning:
E=70 MeV proton beam, I= 750 mA
Production & re-acceleration of exotic beams, from p-induced Fission on UCx
SPES for medicine
SPES Neutron facility
Proposal
Financed
LARAMED & ISOLPHARM projects
Radisotopes for medical applications
Accelerator based neutron source
(Proton and Neutron Facility for Applied Physics)
Michele Ballan

5. What is a radiopharmaceutical?
Radiopharmaceuticals are medicines that deliver a predefined amount of radiation to a target tissue for diagnostic or therapeutic purposes depending on the mechanism of decay
Nuclear medicine applications
Therapeutic agents
Diagnostic agents
Radionuclides properties:
Decay properties
Chemical properties
Half-life
Feasibility of large scale production
Michele Ballan

6. Traditional methods New method: ISOL vs others
Nuclear reactor
Traditional methods
Low specific activity levels
High neutron fluxes required
Irradiation of targets of the same element
→ Isotopic impurities (carrier added - radioisotopes)
Cyclotron
New method:
β- radionuclides can be easily produced as carrier-free isotopes
No nuclear reactor required
Michele Ballan

7. Carrier-added radionuclides
The Specific activity
The specific activity is a measure of the activity per mass and is usually expressed in units of GBq/mg or Ci/mg.
A) Radioisotopes diluted by non therapeutic atoms of the same element have low specific activity.
Carrier-added radionuclides
B) Radioisotopes present only in the mass of the element of interest have high specific activity.
Carrier-free radionuclides
Michele Ballan

8. ISOLPHARM Method overview
The ISOLPHARM method is capable of selecting and isolating a
SINGLE ISOTOPE
→ extremely high specific activity
ISOL
PHARM
Michele Ballan

9. The ISOLPHARM patent Patent title:
The use of ISOL technique for the production of radiopharmaceuticals is a INFN PATENT
Patent title:
«Method for producing beta emitting radiopharmaceuticals and beta emitting radiopharmaceuticals thus obtained»
EU patent
US patent
CANADA patent
Michele Ballan

10. ISOLPHARM (1st phase): produced radionuclides
In target production of 89Sr and 90Y* using a standard UCx target
Already developed and tested!
In target production of 64Cu using a Ni-based target
Under development
Michele Ballan

11. Specific activity (the case of 89Sr)
Traditional production methods (reactor)
New method
Isotopic contamination in the substrate
Isobaric contamination in the substrate
Difficult chemical separation
Easy chemical separation
Low specific activity
High specific activity
~ 0,004 GBq/mg
~ 597 GBq/mg
Michele Ballan

12. Isotope production: UCX target
PPB:
40 MeV, 200 μA b) a)
[nuclide/s] b) a)
Michele Ballan

13. SPES UCX target yield: other isotopes?
A lot of ISOL beams can be potentially produced:
Only a few of the produced isotopes are currently used/studied in nuclear medicine (traditional techniques allow the production of a limited variety of radioisotopes)
Is it possible that other isotopes will be interesting as radiopharmaceuticals “active core”?
Other ISOL isotopes?
ISOLPHARM2
ISOLPHARM isotopes
[nuclide/s]
Michele Ballan

14. Other ISOL Isotopes of medical interest? (light)
Selection criteria
Diagnosis
Theragnostics
Therapy
Michele Ballan

15. Almost 60 ISOL isotopes were found!
Other ISOL Isotopes of medical interest? (heavy)
Almost 60 ISOL isotopes were found!
(up to now)
Diagnosis
Theragnostics
Therapy
Michele Ballan

16. Three target concepts are currently under investigation:
Innovative Target concepts: overview
ISOL production of the desired isotopes requires specific targets.
Targets have to be:
Solid
Refractory (more refractory than the element for which they were designed)
Three target concepts are currently under investigation:
⚛ UCX target (Operation temperature: 2200°C)
⚗ Target R&D and state of art:
☢ Innovative isotopes production: 111Ag
⚛ ZrGe target (Operation temperature: 1800°C)
☢ Innovative isotopes production: As & Ga isotopes
☢ 64/67Cu unexpected production!
⚛ TiC/TiB2 target (Operation temperature: 2000°C)
☢ Innovative isotopes production: Sc isotopes
Nuclear reactions studied
Designed
Tested
Nuclear reactions studied
Designed
Tested
Nuclear reactions studied
Designed
Tested
Michele Ballan

17. 111Ag 64-67Cu 43-44-47Sc SPES TiC target PPB 40 MeV , 200 µA
111Ag, 64-67Cu, Sc production (ISOLPHARM 2)
111Ag
SPES UCx target PPB 40 MeV , 200 µA
64-67Cu
SPES ZrGe target PPB 70 MeV , 100 µA
Up to 2 Ci in target after 5 days!
Up to 40 mCi (67Cu) – 1500 mCi (64Cu) in target after 5 days!
Sc SPES TiC target PPB 40 MeV , 200 µA
Up to 870 mCi (43Sc) – 6450 mCi (44Sc) – 2200 mCi (47Sc) in target after 5 days!
Michele Ballan

18. Activity done so far at LNL - UNIPD-DSF
Beam LNL
Simulation of the process using stable ion beams thanks to the SPES test bench (front-end off-line)
UNIPD-DSF
Extraction from the substrate, quantification and chemical separation of the deposited element
Ion beams produced, deposited, dissolved and analyzed: Sr+, Y+, I+, Cu+ (4 master, 2 PhD. students)
Michele Ballan

19. Conclusions: what’s next?
⚛ Cross check of the Fluka calculated yields using different models (Geant4)
⚛ Performing of the first studies with radioactive ion beams (after )
⚛ Building an ISOLPHARM national community: UNIPD (Industrial Engineering, Pharmaceutical Sciences, Physics & Chemistry Departments), INFN (INFN-PD, INFN-FE, INFN-NL, INFN-TIFPA) and hospitals (Castelfranco Veneto, Reggio Emilia) are involved.
⚛ Building an ISOLPHARM international community: POLATOM (Poland) & NCSR-DEMOKRITOS (Greece) are involved in an European project. Some interest also from PSI & CERN ISOLDE – MEDICIS (Switzerland).
Michele Ballan

20. Thank you for your kind attention
Michele Ballan

21. & to the RIB production group…
22/04/2018
& to the RIB production group…
Michele Ballan