The new Bern cyclotron laboratory for PET radioisotope production and its beam line for multi-disciplinary research

Saverio Braccini Albert Einstein Center for Fundamental Physics Laboratory for High Energy Physics (LHEP) University of Bern

Outline

>! The SWAN Project in Bern

>! Positron Emission Tomography (PET) and Fluordesoxyglucose (FDG)

>! The cyclotron laboratory for PET radioisotope production and research

>! Commissioning of —! Cyclotron, targets, FDG production —! The research Beam Transfer Line (BTL)

>! First research activities with the BTL —! Radiation protection —! Beam monitoring detectors

>! Conclusions and outlook

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The SWAN Project in Bern

>! Initiated in 2007 by the Inselspital and the University of Bern

>! SWAN stands for SWiss hAdroNs >! Aims:

1.! Production of radiopharmaceuticals, for PET diagnostics in particular

2.! Proton therapy 3.! Multi-disciplinary research

>! Phases: 1.! Cyclotron laboratory for radioisotope production and research 2.! Proton therapy centre

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The structure of SWAN

>! SWAN is based on the synergy between public institutions and private investors

SWANtec Holding AG

SWAN Isotopen AG

SWAN Hadron AG

Uni Bern Inselspital

SWISS HADRON FOUNDTION

Founded in 2010 Aims: •! Research •! Compassionate treatment

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Cyclotron laboratory in operation !

Proton therapy centre under study

Present status of the project

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Positron Emission Tomography (PET)

•! Functional imaging (metabolism)

•! 18F is the most used radioisotope: 18O (p,n) 18F

•! FDG is the most used radiotracer (18F : T1/2 = 110 min.)

•! FDG follows glucose metabolism

Cyclotron PET tomograph

PET image

Gamma ray detectors (Ex. BGO, LSO crystals)

CT-PET

Radiopharmacy Protons

~15-20 MeV, ~100 µµA

FDG synthesis

2-deoxy-2-[18F]fluoro-D-glucose (18FDG)

C

O

H

D-glucose : CH2OH (CHOH)4 CHO 18F

Example of PET imaging

•! PET is both a clinical and a research tool •! ! and cyclotrons for the production of PET isotopes have a high multi-disciplinary research potential !

The construction in 2009 !

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! and in 2010 !

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A multi-function building

Construction of the cyclotron bunker June 2010

The cyclotron rigging June 2011

Oncology

Nuclear Medicine

Offices and cold labs

Cyclotron, beam line, technical area and labs

Hot labs for production and research

May 2012

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The hot labs

Production 1

Production 2

(Production 3)

Quality Control

Research (UniBern)

>! 3 GMP production labs (FDG, 18F compounds, future developments) >! One multi-function research lab (Prof. A. Türler – UniBern and PSI) >! Hotcells by TEMA Sinergie (Italy) DPNC - Genève - 27.02.2013 - SB 12

GMP production radiopharmacy labs

>! Fully automated 18-FDG GMP production

Synthesis modules

Dispensing unit

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The radiochemistry and radiopharmacy research lab

Laboratory Technical area (back of the hotcells)

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The cyclotron and the Beam Transport Line (BTL)

>! IBA 18 MeV “twin” high current cyclotron (two H- ion sources, extraction by stripping)

>! 7 out ports (4 18F liquid targets, 1 15O gas target, 2 spare)

>! External beam line in a separate bunker: production and research in parallel

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Commissioning of the cyclotron and Site Acceptance Tests (SATs)

>! First beams February 7th, 2012 >! Optimization of the cyclotron

—! Ion sources —! Central region (B field) —! Radio frequency —! Control system (software)

>! High current tests on beam dump —! 150 µA on target for 4 hours with both ion sources (single beam) —! 75 µA + 75 µA on target (dual beam) —! 100 µA + 50 µA on target (asymmetric dual beam)

>! 18F and FDG production (4 targets) —! 9.6 Ci of 18F in single beam (2 hours of irradiation at 80 µA) —! 13.5 Ci (500 GBq) of 18F in "80 minutes (75 µA +75 µA – dual beam) —! FDG with yield >60%

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The Beam Transport Line (BTL)

>! Research and training activities: novel detectors, radiation biophysics, radioprotection, radiochemistry, radio-pharmacy, material sciences, !

>! Low currents (1 µA – 1 nA) and high currents (up to 150 µA) >! Beam spots on target: from " 5 mm to 20 mm diameter >! BTL: 6 m long, 2 quadrupole doublets, neutron shutter DPNC - Genève - 27.02.2013 - SB 17

The original industrial design of the BTL

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Cyclotron

XY Steering

Stripper

BTL commissioning and optimization

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>! Requirement: transmission >95% >! For an optimal transmission:

—! Beam centered within " 1 mm —! Beam parallel within " 1 mrad with respect to the optical axis

>! This is achieved by —! Changing the radial position and azimuth angle of the stripper —! Changing the currents in the XY Steering magnet

! Alignment is crucial ! The radial position of the

stripper is critical ! The position of the steering

magnet is critical ! Beam monitoring is essential

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Position of the XY Steering magnet: a simulation study (BeamLineSimulator)

>! Assumptions: •! Beam centred in position 1 (measured with beam viewer) •! Tilt of 7 mrad with respect to the optical axis (calculated value)

>! Distortion effects may be relevant! (steering effects of the quads) >! Steering magnet-beam viewer swap: negligible distortion

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1 2 Actual 1)!Beam viewer 2)!XY Steering

1 2 Optimized 1)!XY Steering 2)!Beam viewer

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Optimized BTL – New design

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>! X-Y steering magnet near the cyclotron >! Stripper radial position optimized (+5 mm) >!Transmission of "97% at 150 µA stable for 60 minutes has been obtained >! Transmission "99% at 10 µA and "100% at 1 µA or less

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BTL commissioning at low currents

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Beam current " 1 µA

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Radiation protection

>! Radiation Protection Monitoring System (RPMS) —! " 40 sensors

>! On line measurement of —! Dose rate due to gamma and neutron radiation —! Air contamination

>! The RPMS is a safety and a research tool

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Air contamination

>! Detectors: —! Incorporation probe embedded in the hand-feet monitors —! Specific sensors on the ducts of the bunker and on the main exhaust

–! 1000 cm2 large surface coupled proportional counters –! Optimized for the detection of betas –! Sensitivity: " 10 Bq/m3

>! A weekly/monthly/yearly balance has to be provided to the Swiss authorities (BAG)

>! Swiss law: 233 Bq/m3 in average can be exhausted into the atmosphere —! In our case " 20000 m3/h are exhausted from the main exhaust —! This corresponds to a weekly balance of 780 MBq —! Alarm threshold set at 70 kBq/m3

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Air contamination measurements during the production of 18F

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A.! Background (no beam) B.! Irradiation - 18F production on liquid target - 150 µA dual beam - 41Ar production C.! Transfer of 18F with 13N release (critical!) D.! FDG synthesis

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Air contamination measurements by extracting the beam into air

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m3 /h

Time

kBq/

m3 >! Beam intensity in air

30-50 nA

>! Irradiations of 60 seconds to test different exit windows

>! Clear signal of air contamination in the main exhaust!

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Air contamination measurements by extracting the beam into air

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Considered reactions: 14N(p, !)11C (Dominant! Larger cross section +larger amount of N2) 16O(p, !)13N

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An interesting measurement !

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Beam viewer 2

Beam monitoring near the target

Four finger collimator

Collimator

Beam dump

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>! Designed for !! Radioisotope production !! Currents > 1 µA

>! Other applications? >! Lower currents (nA)?

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A beam monitor detector based on doped silica and optical fibres

>! Goal: general purpose device for low currents (nA) and high currents (µA), continuous and pulsed beams

>! Principle: a sensing fibre is moved through the beam >! For details: S. Braccini et al., 2012 JINST 7 T02001 and arXiv:1110.1583

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Construction of the doped silica sensing fibres at the IAP of Uni Bern

M. Neff et al., Optical Materials 31 (2008) 247–251

>! Sensing fibre: good light yield + heat and radiation resistant

>! Developed for laser applications

>! Relatively simple method using a pre-form filled with granulated oxides

>! Possible dopants: Ag, Pb, Sb, Ta, ...

>! Sb3+ (0.5%) doped fibres selected

>! 500 µm diameter

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Beam tests with the 2 MeV RFQ linac at LHEP

The first prototype detector

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UniBeAM installed on the BTL

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>! New remotely controlled motorized device >! New Sb, Ta and Ce doped fibres >! Photodiode + PM readout, radiation hardness studies

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Very first beam tests

>! Beam intensity 1 µA

>! Clear reproducible signal due to left-right and right-left successive sweeps

>! Studies under way on radiation hardness, signal vs temperature, signal vs beam intensity, etc !

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Collaboration with the radiation protection group at CERN

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>! Test of the electronics (radiation hardness)

>! Study of GEM based beam profile monitors

>! Study on air activation by means of Medipix detectors

>! Study of thermal and fast neutron fluxes

>! Studies of the activation of materials used in medical accelerators

>! Work partially supported by EU projects

First tests with Medipix detectors

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>! Very first set-up: one “Naked” Timepix located in front of the beam and one Si Timepix located at 90°

>! Medipix: 256#256 Si pixel sensors (total area 14.08 mm # 14.08 mm)

>! Timepix: gives timing information

>! Particle discrimination

First preliminary results with the detector at 90o

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>! Effects due to neutron interactions are clearly visible

>! Air activation: clear signals from gamma and beta radiation

Beam monitoring Instrument based on Secondary Emission (BISE)

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>! Non destructive beam monitoring

>! On-line image of the beam

>! nA range (hadrontherapy) and µA range (isotope production)

>! Sensors: MCP, MCS, silicon detectors

A unique gamma source ?

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Hafele et al., Phys.Rev.B 135(1964)365

>! 40Ca is “double magic” (very stable)

>! A gamma energy larger than the proton energy can be released!

>! This method is promising to produce resonant gamma rays in the 20-24 MeV energy range

>! Use: study and calibration of scintillator crystals

Conclusions

>! The new cyclotron laboratory for radioisotope production and research in Bern has been constructed and commissioned

>! A specifically conceived beam line allows multi-disciplinary research in parallel with PET radioisotope production

>! The first research activities are starting in parallel with FDG

production —!Detector and accelerator physics —!Radiation protection

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Outlook

We are looking forward to interesting research

and fruitful collaborations !

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