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JRC MC40 and Nanoparticle Activation JRC MC40 and Nanoparticle activation DKFZ – Heidelberg on 13 May 2011 – Cyclotron Anniversary Meeting 1 Joint Research Centre (JRC) Antonio Bulgheroni on behalf of the cyclotron team IHCP - Institute for Health and Consumer Protection Ispra - Italy http://ihcp.jrc.ec.europa.eu/ http://www.jrc.ec.europa.eu/ Summary DKFZ – Heidelberg on 13 May 2011 – Cyclotron Anniversary Meeting 2 • The JRC MC40, very brief intro and history – Details on the 6 target systems. – What was the cyclotron doing in the last 30 years • Radioactive nanoparticle – What makes nano different – Lack of knowledge, lack of policies – Radioactivity as a tracer: the good and the bad • How to survive other 20 years? – Living spare parts! • Conclusions The JRC MC40 DKFZ – Heidelberg on 13 May 2011 – Cyclotron Anniversary Meeting 3 Updated parameters Particles Minimum Energy Maximum Energy Maximum Extracted (MeV) (MeV) Current (µA) p 8 39 60 α 8 39 30 3He2+ 8 53 30 d 4 19.5 60 • 7 beam lines in 3 (almost) independent irradiation halls – 6 installed beam lines – 1 beam line in maintenance (BL 3) – 2 halls sharing the same shielding door • CZ laboratories – Radiochemestry – Biology – Radiopharmaceuticals production clean rooms BL Specifications / 1 DKFZ – Heidelberg on 13 May 2011 – Cyclotron Anniversary Meeting 4 Beam Line 1: Cross section • Thin / thick foils • Not exceeding 1 microA • No cooling at all • No entrance window, target directly in vacuum Beam Line 2: General purpose • Solid and powder target • Up to 30 microA of current • Either water or helium cooling • 600 micron Al + 2 mm of coolant in front of target DKFZ – Heidelberg on 13 May 2011 – Cyclotron Anniversary Meeting BL Specifications / 2 • Beam Line 3: Production • Liquid target • High power Water cooling 5 MAINTENANCE • Beam Line 4: F-18M productionAINTENA (GE)N • Liquid target • Around 50 microA • Helium + Water cooling 2 runs per night, 300 GBq each BL Specifications / 3 DKFZ – Heidelberg on 13 May 2011 – Cyclotron Anniversary Meeting 6 Beam Line 5: ARC neutron activator • Collaboration with AAA • Berillium target with graphite moderator around • Water cooled • Neutron flux around 1E10 Beam Line 6: Hi-power solid target • Solid target (foils or powder) • He + water cooling cooled • Around 600 micron Al in front of target • Up to 50 microA @ 38 MeV p • Pneumatic remote transfer to hot cell Cyclotron life DKFZ – Heidelberg on 13 May 2011 – Cyclotron Anniversary Meeting 7 3 1980 1990 2000 2010 1 0 2 Sorin - 123I GE HealthCare FDG 1982 1986 Commis. license Commercial production of medical radioisotopes 1991 2001 2003 2012 1998: IAM→IHCP Radiation damage – fission and fusion materials Radioisotopes for Nuclear Medicine s a Thin Layer Activation for wear and corrosion e r studies, release from biomedical materials a h c Accelerator driven neutron r a activator (ARC) - AAA e s e Radioactive Nano- r ≥ 90% of our research particles y e K = Hand over to other institute Nano: what’s the difference? DKFZ – Heidelberg on 13 May 2011 – Cyclotron Anniversary Meeting 8 • Large specific surface 0,8 s • Chemical reactivity very e l u different compared to bulk c 0,6 Specific Surface e l material o M • Quantum effects lead to e c a 0,4 f special properties r u S (electronic, mechanical, f o 0,2 optical …) o i t • Matrix dependent properties a R • Many forms: fullerenes, 0 nanotubes, nanocarriers, 0 10 20 30 40 50 60 nanoemulsions, Size [nm] -encapsulates Nano in everyday life already DKFZ – Heidelberg on 13 May 2011 – Cyclotron Anniversary Meeting 9 Nanotechnology is Nanotech everywhere •production, •manipulation •use of materials with one size of 100 nanometers or less. At this scale, common materials exhibit properties that differ physically, chemically and biologically from their larger counterparts. Medicine Associated risks? Nanotoxicity challenges DKFZ – Heidelberg on 13 May 2011 – Cyclotron Anniversary Meeting 10 Toxicity of industrially manufactured nanomaterials and nanoparticles What a toxicologist DOES want: – Industrially made NP, not your own lab production – Minimum invasive labelling technique What a toxicologist does NOT want: – Any surface change, because of the way the NP interacts with cell – Any structural change in the NP crystal DKFZ – Heidelberg on 13 May 2011 – Cyclotron Anniversary Meeting •Radiotracer principle – Minimum requirements on Why radioactive nanoparticles? • – specimen preparation High Imagingsensitivity option •No NP surface change Other applications: • • nuclear medicine (diagnosis, dosimetry, therapy) • industrial process control materials R&D n • o 1 Courtesy W. Kreyling et al. ti n te e 0.1 r rs In vitro cellular uptake u • o 0.01 -h 4 TiO2-inhalation data corrected for fast clearance 2 0.001 In vivo biokinetics and 0.0001 biodistribution Lunge+BAL Herz Haut Leber Milz Nieren Kopf Gehirn Restl Körper organs 11 Muskel Knochen Blut Uterus Urin Neutron activation (reactors) Ion activation (accelerators) What can we label? DKFZ – Heidelberg on 13 May 2011 – Cyclotron Anniversary Meeting 12 NP target system DKFZ – Heidelberg on 13 May 2011 – Cyclotron Anniversary Meeting 13 • 300 µm entrance window • 400 µm “target thickness” • typical payload 20-30 mg • front and rear side cooling • water cooling or refrigerated He 48Ti(p,n)48V Ep,cycl = 23.5 MeV Ep,TiO2= 14.5 MeV How is ion-beam labelling working? DKFZ – Heidelberg on 13 May 2011 – Cyclotron Anniversary Meeting 14 • Where is the label going? – Recoiling implantation after nuclear reaction – Requires assessment of leaching tests to prove label is sticking to 20 nm the NP – Requires irradiation of dry powder (we failed in activating nano solution with ion beams) – The recoiling label is passing through a certain number of NPs causing radiation damage Radiation damage DKFZ – Heidelberg on 13 May 2011 – Cyclotron Anniversary Meeting 15 • Primary proJectiles – All protons passing through the target material • Recoiling labels – One for each nuclear reactions (small number compared to primary particles) – Hugh mass and charge High LET • Specific to the last NP – Possibly more damaged to due Bragg peak – Of particular interest since it is the one to be observed in experiments. Reference figures for TiO2 after 100 microAh Primary DPA 6.7 E-3 Annealing due to local thermal Recoiling DPA 1.1 E-3 heating Extra DPA (last NP) 2.3 E-3 Thermal damage / 1 DKFZ – Heidelberg on 13 May 2011 – Cyclotron Anniversary Meeting 16 • NP powder behaves like air for thermal conductivity – No or few thermal bridges between neighbour NP – External target cooling NOT preventing internal warming – Parabolic shape assumption based on fixed temperature capsule walls and linear energy deposition – Limiting max current for irradiation • Temperature control at nanoscale for nanoseconds – NP crossed by recoiling nuclei thermal spike – Temperature increase depends on NP size – Risk of melting/evaporation and re-crystallization Thermal damage / 2 DKFZ – Heidelberg on 13 May 2011 – Cyclotron Anniversary Meeting 17 • Clear effect in temperature sensitive NP like TiO2 – Phase change from Anatase to Rutile – Melting point at 1850 C, but effects like agglomeration and particle growth starts much earlier (150 C). XRD spectrum 160 140 ST01 - Cold 120 ST01 - 25uA - 19 MeV Rutile 100 80 60 40 20 0 0 10 20 30 40 50 60 70 80 90 100 -20 2*theta Conclusions DKFZ – Heidelberg on 13 May 2011 – Cyclotron Anniversary Meeting 18 • The JRC MC40 has never been used so much as in the last years • Routine radio-isotope production is supporting interesting nano-bio applied research programs. • Radiolabelling is an effective technique for in vivo and in vitro nanotoxicity studies – There is a number of possible problems, but none of them is a show- stopper for the case of radioactive NP – Can be used also for other applications • Several labs around Europe requesting radio-NP for their experiments Spare parts DKFZ – Heidelberg on 13 May 2011 – Cyclotron Anniversary Meeting 19.
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