After 25 years of successful research in the nuclear and radiation physics domain, the KVI-CART research center in Groningen is upgraded and re-established as the PARticle Therapy REsearch Center (PARTREC). Using the superconducting cyclotron AGOR and being embedded within the University Medical Center Groningen, it operates in close collaboration with the Groningen Proton Therapy Center. PARTREC uniquely combines radiation physics, medical physics, biology and radiotherapy research with an R&D program to improve hadron therapy technology and advanced radiation therapy for cancer. A number of further upgrades, scheduled for completion in 2023, will establish a wide range of irradiation modalities, such as pencil beam scanning, shoot-through with high energy protons and SOBP for protons, helium and carbon ions. Delivery of spatial fractionation (GRID) and dose rates over 300 Gy/s (FLASH) are envisioned. In addition, PARTREC delivers a variety of ion beams and infrastructure for radiation hardness experiments conducted by scientific and commercial communities, and nuclear science research in collaboration with the Faculty of Science and Engineering of the University of Groningen

Barazzuol, L.

Both, S.

Brandenburg, S.

Coppes, R.P.

Dendooven, P.

Gerbershagen, A.

Jones, B.N.

Schippers, J.M.

van der Graaf, E.R.

van Goethem, M.-J.

van Luijk, P.

English

After 25 years of successful research in the nuclear and radiation physics domain, the KVI-CART research center in Groningen is upgraded and re-established as the PARticle Therapy REsearch Center (PARTREC). Using the superconducting cyclotron AGOR and being embedded within the University Medical Center Groningen, it operates in close collaboration with the Groningen Proton Therapy Center. PARTREC uniquely combines radiation physics, medical physics, biology and radiotherapy research with an R&amp;D program to improve hadron therapy technology and advanced radiation therapy for cancer. A number of further upgrades, scheduled for completion in 2023, will establish a wide range of irradiation modalities, such as pencil beam scanning, shoot-through with high energy protons and SOBP for protons, helium and carbon ions. Delivery of spatial fractionation (GRID) and dose rates over 300 Gy/s (FLASH) are envisioned. In addition, PARTREC delivers a variety of ion beams and infrastructure for radiation hardness experiments conducted by scientific and commercial communities, and nuclear science research in collaboration with the Faculty of Science and Engineering of the University of Groningen

ARTS repository - University of Groningen

   University of GroningenEstablishment of the New Particle Therapy Research Center (PARTREC) at UMCGGroningenGerbershagen, A.; Barazzuol, L.; Brandenburg, S.; Coppes, R.P.; Dendooven, P.; vanGoethem, M.-J.; van der Graaf, E.R.; Jones, B.N.; van Luijk, P.; Schippers, J.M.Published in:HIAT 2022 - International Conference on Heavy Ion Accelerator Technology 2022DOI:10.18429/JACoW-HIAT2022-MO3C2IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite fromit. Please check the document version below.Document VersionPublisher's PDF, also known as Version of recordPublication date:2022Link to publication in University of Groningen/UMCG research databaseCitation for published version (APA):Gerbershagen, A., Barazzuol, L., Brandenburg, S., Coppes, R. P., Dendooven, P., van Goethem, M-J., vander Graaf, E. R., Jones, B. N., van Luijk, P., Schippers, J. M., & Both, S. (2022). Establishment of the NewParticle Therapy Research Center (PARTREC) at UMCG Groningen. In HIAT 2022 - InternationalConference on Heavy Ion Accelerator Technology 2022 (pp. 20-23) https://doi.org/10.18429/JACoW-HIAT2022-MO3C2CopyrightOther than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of theauthor(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).The publication may also be distributed here under the terms of Article 25fa of the Dutch Copyright Act, indicated by the “Taverne” license.More information can be found on the University of Groningen website: https://www.rug.nl/library/open-access/self-archiving-pure/taverne-amendment.Take-down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediatelyand investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons thenumber of authors shown on this cover page is limited to 10 maximum.ESTABLISHMENT OF THE NEW PARTICLE THERAPY RESEARCHCENTER (PARTREC) AT UMCG GRONINGENA. Gerbershagen∗ , 1, L. Barazzuol1, 2, S. Brandenburg 1, R.P. Coppes 1, 2, P. Dendooven1,M.-J. van Goethem1, E.R. van der Graaf1, B.N. Jones1, 2, P. van Luijk1, 2, J.M. Schippers1, S. Both11 Particle Therapy Research Center (PARTREC), Department of Radiation Oncology,University Medical Center Groningen, University of Groningen, The Netherlands2 Department of Biomedical Sciences of Cells and Systems, University MedicalCenter Groningen, University of Groningen, Groningen, The Netherlands.AbstractAfter 25 years of successful research in the nuclear andradiation physics domain, the KVI-CART research center inGroningen has been re-established as the PARticle TherapyREsearch Center (PARTREC). Using the superconductingcyclotron AGOR and being embedded within the UniversityMedical Center Groningen, it operates in close collaborationwith the Groningen Proton Therapy Center.PARTREC uniquely combines radiation physics, medicalphysics, biology and radiotherapy research with an R&D pro-gram to improve hadron therapy technology and advancedradiation therapy for cancer. A number of further upgrades,scheduled for completion in 2023, will establish a widerange of irradiation modalities, such as pencil beam scan-ning, shoot-through with high energy protons and SpreadOut Bragg Peak (SOBP) for protons, helium and carbonions. Delivery of spatial fractionation (GRID) and doserates over 300 Gy/s (FLASH) are envisioned. In addition,PARTREC delivers a variety of ion beams and infrastructurefor radiation hardness experiments conducted by scientificand commercial communities, and nuclear science researchin collaboration with the Faculty of Science and Engineeringof the University of Groningen.PARTREC FACILITYThe PARticle Therapy REsearch Center (PARTREC) is anewly established research facility at the University MedicalCenter Groningen (UMCG). It builds on the success of theformer KVI-CART research center and utilizes the super-conducting cyclotron AGOR (see Fig. 1) for experimentalresearch, mainly in radiation physics and biology.Built by a French-Dutch collaboration in Orsay in theperiod 1987 – 1994 and commissioned in Groningen in1996, AGOR operated within the KVI-CART research cen-ter [1]. It was used for 25 years to perform research in nuclearphysics and on fundamental symmetries [2] as well as fordetector development, radiation hardness testing [3,4] and ra-diobiological experiments. Recently besides nuclear physics,radiation and accelerator physics and radiobiology,the re-search focus has been shifting towards medical applicationsand therefore the facility and its personnel was integrated intothe University Medical Center Groningen (UMCG). Hence,∗ a.gerbershagen@umcg.nlFigure 1: Photograph of the AGOR accelerator.the new structure, additional goals and the new infrastruc-ture (described in the chapters below) have been formalizedvia a creation of the new research center named PARTREC(logo in Fig. 2) was created.Working in close collaboration with the UMCG Gronin-gen Proton Therapy Center (GPTC), PARTREC research ac-tivities encompass medical physics, radiation biology exper-iments, tests of different radiation therapy treatment modal-ities and development of detector technology. In addition,it provides opportunities for experiments in the domain ofradiation hardness, for both the scientific and commercialcommunities, and nuclear science, in collaboration with theFaculty of Science and Engineering of the University ofGroningen.Figure 2: Logo of new PARticle Therapy REsearch Center(PARTREC).BEAM DELIVERY CAPABILITIESThe magnetic field of AGOR has a varying value between1.7 to 4.1 T. It is produced by two superconducting maincoils and fifteen trim coils for the precise field shaping, withthree iron hill sectors for focussing and defocussing of thecirculating beam (see Fig. 3).15th Int. Conf. on Heavy Ion Acc. Technology HIAT2022, Darmstadt, Germany JACoW PublishingISBN: 978-3-95450-240-0 ISSN: 2673-5547 doi:10.18429/JACoW-HIAT2022-MO3C2MO3C2ContentfromthisworkmaybeusedunderthetermsoftheCCBY4.0licence(©2022).Anydistributionofthisworkmustmaintainattributiontotheauthor(s),titleofthework,publisher,andDOI20 Applications: Medical, Materials, Isotopes, Space and othersFigure 3: Schematic 3D-model of the AGOR cyclotron inte-rior.The acceleration is performed by three halfwave RF cavi-ties, which can be mechanically extended or contracted toproduce accelerating frequencies of 24–62 MHz with the har-monic numbers of h = 2, 3 or 4. The beam is axially injectedfrom three external ion sources, with two ECR sources forheavy ions and a multi-cusp source for light ions. The extrac-tion happens after 300–500 turns, depending on harmonicmode. The extraction radius is about 870–890 mm (depend-ing on E/A of the beam), with the turn separation at theextraction being in the order of 2–3 mm, which correspondsto the width of the beam.Given the flexibility of the magnetic field, RF frequencyand ion sources, AGOR routinely delivers ion beams of allstable elements up to xenon, within an energy range depen-dent on the charge-to-mass ratio of the ions. For radiationhardness tests, the facility provides beams of protons at dif-ferent primary energies and various ions (from He to Xe)at 30 MeV/amu (see diagram in Fig. 4 and setup in Fig. 5).Experiments can be performed at 90 MeV/amu with ionsup to Ne. The changeover between the different particletypes at the same energy per amu takes typically less thanan hour. The possibilities of extending the palette of beamstowards still heavier fully stripped ions and lower energies,as suggested by Fig. 4, are under examination [5].Proton beams with energies relevant for clinical purposes(range in water up to 230 mm) are used for preclinical ra-diation biology research and proton therapy related physicssince twenty-five years. They can be delivered with the con-tinuous intensity of up to 109 particles per second per cm2with the dose homogeneity level within 1% for a scannedFigure 4: Ion types provided by AGOR, with their extractionenergy plotted as function of their charge-over-mass-ratio.Figure 5: Photograph of the setup for heavy ion irradiations.beam and within 2-10% for scattered beams, dependent onthe irradiation field size. The intensity of the heavier ionbeams depends on the ion type and can be varied in the range102-105 ions / (s cm2), with the field homogeneities compa-rable to the ones of proton beams. The LET can be tuned bymeans of a degrader system just before the sample location.The beam purity is very high (contamination below 10−5)and is verified by means of a silicon detector telescope thatstops the ions and provides particle identification.RESEARCH PLANS WITH THENEW INFRASTRUCTURETo extend PARTREC’s research capabilities, new infras-tructure is currently under development and is expected tobecome available in 2023.This includes design, installation and commissioning ofa new beam line for the biomedical research, which willfree up additional capacities at the existing beam line (seeFig. 6). The new irradiation modalities developed in theframework of this extension will also become available atthe existing beam line. These include scattering and pencil15th Int. Conf. on Heavy Ion Acc. Technology HIAT2022, Darmstadt, Germany JACoW PublishingISBN: 978-3-95450-240-0 ISSN: 2673-5547 doi:10.18429/JACoW-HIAT2022-MO3C2Applications: Medical, Materials, Isotopes, Space and othersMO3C221ContentfromthisworkmaybeusedunderthetermsoftheCCBY4.0licence(©2022).Anydistributionofthisworkmustmaintainattributiontotheauthor(s),titleofthework,publisher,andDOIFigure 6: Photograph of the setup for radiobiological irradi-ations.beam scanning, shoot-through with high energy protons aswell as Spread-Out Bragg Peak for protons and helium. Ad-ditionally, the adaptation of the facility for the delivery ofspatial fractionation and high dose rates in excess of 300 Gy/s(FLASH) is maturing. An active Proton Radiography pro-gram with a variety of detectors in collaboration with GPTCexists and advanced detector technologies, such as PET scan-ner panels around a head-shaped phantom [6,7] for the op-timization of margins for head-and-neck tumour treatment,are under development (see Fig. 7).Figure 7: Experimental setup showing the head phantomin-between the 2 PET scanner panels. The head phantom sitson top of 2 orthogonal translation stages and a rotation stage.The direction of the proton beam is indicated by the arrow.The proton beam will be scanned vertically and horizontallywith respect to this direction. The proton beam direction andentry point in the head phantom can be accurately controlledby combined translation and rotation of the phantom.New experimental research [8] on the production ofneutron-rich heavy nuclei using multi-nucleon transfer reac-tions between heavy nuclei (e.g. 136Xe on 208Pb) has recentlybeen started. An upgrade to one of the electron cyclotronresonance (ECR) ion sources is under development, in addi-tion to the work on improvement of transmission from theion source to the cyclotron extraction. A new experimentalstation consisting of a 3 T superconducting solenoid frag-ment separator and MR-ToF mass spectrometer is developedin collaboration with the University of Groningen.The new infrastructure will allow us and our users toaddress various research questions such as:• Radiation effects on electronics.• Testing of particle detectors [9].• Biological and physical radiation effects in space.• Studies of radiation sensitivity variations within normaltissue and tumour.• Mechanistic studies using various tumour and normaltissue utilizing in vitro and in vivo models to investigateinteraction between radiation and systemic treatments,such as chemotherapy, immunotherapy and DNA dam-age response (DDR) modulators.• LET and RBE studies for biological treatment planning.• Advanced radiotherapy dose delivery techniques, suchas GRID and FLASH.• Therapeutic window optimization and translation to theclinic.Medium-term, it is envisaged for PARTREC to provideusers a one-stop-shop facility. This implies that PARTRECwill support the users during the complete process of exper-iment development, the actual irradiation and its follow-up.For the animal irradiations, PARTREC will guide the userswith the ethics authorisation process, animal procurementlogistics, and will provide on-site animal accommodationwith individually ventilated cage (IVCs) with a capacity of200 rats and mice. For the follow-up the laboratory for ani-mal handling prior and post irradiation could be used. TheGronSAI imaging center will provide the possibilities toperform optical, structural and functional imaging of theanimal models prior and post irradiation using fluorescence,bioluminescence, PET, CT, MR and multi-modality imagingsystems. In addition, the local data management facilitiescould be used to store, process and analyze the irradiation-related data.CONCLUSIONThe new PARTREC facility will provide the physics, radi-ation hardness, radiation biology and medical communitieswith a state-of-the-art, open access research infrastructure forcell/tissue culture and small animal research. The upgradesto the infrastructure will become available from 2023.ACKNOWLEDGEMENTResearch at PARTREC is supported by the Dutch Can-cer Foundation KWF, the Dutch Organization for ScientificResearch NWO, the European Union, the European SpaceAgency ESA, Ion Beam Applications S.A., RaySearch Lab-oratories, Siemens Healthineers AG, the University MedicalCenter Groningen and the University of Groningen.PARTREC is a member of RADNEXT, INSPIRE, CORA-IBER, ARIEL and COST irradiation networks.15th Int. Conf. on Heavy Ion Acc. Technology HIAT2022, Darmstadt, Germany JACoW PublishingISBN: 978-3-95450-240-0 ISSN: 2673-5547 doi:10.18429/JACoW-HIAT2022-MO3C2MO3C2ContentfromthisworkmaybeusedunderthetermsoftheCCBY4.0licence(©2022).Anydistributionofthisworkmustmaintainattributiontotheauthor(s),titleofthework,publisher,andDOI22 Applications: Medical, Materials, Isotopes, Space and othersREFERENCES[1] S. Galès for the AGOR project group, “AGOR: A supercon-ducting cyclotron for light and heavy ions”, in Proc. ICCA’11,Tokyo, Japan, Oct. 1989, paper f01, pp. 184–190.[2] H. W. Wilschut and K. Jungmann, “Trapped Radioactive Iso-topes: micro-laboratories for fundamental Physics (TRIµP)”,Nuclear Physics News, vol. 17, no. 1, p. 11-15, 2007. doi:10.1080/10506890701225114[3] E.R. van der Graaf, R.W. Ostendorf, M.-J. van Goethem,H.H. Kiewiet, M.A. Hofstee, and S. Brandenburg, “AGOR-FIRM, The AGOR Facility for Irradiations of Materials”, inProc. RADECS 2009, p. 443, 2010. doi:10.1109/RADECS.2009.5994694[4] F. Diblen, T. Buitenhuis, T. Solf, P. Rodrigues, E. van der Graaf,M. J. van Goethem, S. Brandenburg, and P. Dendooven, “Radia-tion hardness of dSiPM sensors in a proton therapy radiation en-vironment”, IEEE Transactions on Nuclear Science, vol. 64, no.7, pp. 1891–1896, 2017. doi:10.1109/TNS.2017.2705522[5] B.N. Jones, S.Brandenburg, and M.-J. van Goethem,“AGOR status report”, in Proc. Cyclotrons’19, Cape Town,South Africa, Sep. 2019, pp. 256–258. doi:10.18429/JACoW-Cyclotrons2019-TUC03[6] I. Ozoemelam, E.R. van der Graaf, M.-J. van Goethem, M. Ka-pusta, Nan Zhang, S. Brandenburg, and P. Dendooven, “Feasi-bility of quasi-prompt PET-based range verification in protontherapy”, Phys. Med. Biol., vol. 65, no. 24, p. 245013, 2020.doi:10.1088/1361-6560/aba504[7] I. Ozoemelam, E.R. van der Graaf, M.-J. van Goethem, M. Ka-pusta, Nan Zhang, S. Brandenburg, and P. Dendooven, “Real-Time PET Imaging for Range Verification of Helium Radio-therapy”, Front. Phys., vol. 8, p. 431, 2020. doi:10.3389/fphy.2020.565422[8] X. Chen et al., “Stacked-ring ion guide for cooling and bunch-ing rare isotopes”, Int. J. Mass Spectrom., vol. 477, p. 116856,2022. doi:10.1016/j.ijms.2022.116856[9] T. Teichmann, M.J.G. Torres, M.-J. van Goethem, E.R. vander Graaf, J. Henniger, A. Jahn, H.H. Kiewiet, M. Sommer,W. Ullrich, C. Weinhold, and T. Kormoll, “Dose and doserate measurements in proton beams using the luminescenceof beryllium oxide”, J. Instrum., vol. 13, p. 10015, 2018. doi:10.3389/fphy.2020.56542215th Int. Conf. on Heavy Ion Acc. Technology HIAT2022, Darmstadt, Germany JACoW PublishingISBN: 978-3-95450-240-0 ISSN: 2673-5547 doi:10.18429/JACoW-HIAT2022-MO3C2Applications: Medical, Materials, Isotopes, Space and othersMO3C223ContentfromthisworkmaybeusedunderthetermsoftheCCBY4.0licence(©2022).Anydistributionofthisworkmustmaintainattributiontotheauthor(s),titleofthework,publisher,andDOI

Establishment of the New Particle Therapy Research Center (PARTREC) at UMCG Groningen

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Establishment of the New Particle Therapy Research Center (PARTREC) at UMCG Groningen

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