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Objectives: Proton therapy, while highly effective and successful, still lacks a key feature: the ability to assess, in-vivo, the dose and end-point location of irradiations. Known as proton range verification, this capability can be realized by incorporating positron emission tomography (PET) systems in both conventional and emerging modalities, such as FLASH proton therapy. FLASH itself may revolutionize radiation oncology with its purported ability to better spare healthy tissues, but only if the underlying mechanisms can be understood. We summarize our work towards establishing in-beam PET modalities and elucidating the mystery of the FLASH effect. Materials: We've developed a PET scanner designed for live, in-beam imaging during therapeutic proton irradiations that can use short-lived positron emitting species (PES) activated by the beam to validate the range and dose of proton depositions. This scanner is made up of PET modules consisting of arrays of LYSO (lutetium-yttrium oxyorthosilicate) scintillating crystals coupled one-to-one to silicon photomultiplier (SiPM) arrays. These modules are readout by electronics based on the TOFPET2 ASIC platform from PETsys Electronics. Methods: Our collaboration with MD Anderson Cancer Center has given us opportunities to take real in-beam data using a non-clinical beamline capable of delivering FLASH proton irradiations into target phantoms made of polymethyl methacrylate (PMMA), high density polyethylene (HDPE), and water. Data collected both during and afterirradiations were used to perform novel analyses and to reconstruct images of PES activity due to the beam. Results: Exploratory studies, using a subset of our PET scanner, have demonstrated successful data acquisition during and after FLASH beam spills including quantitative imaging and dosimetry of activated phantoms. The full results, explored in this work, are highly promising and prove that in-beam PET can deliver on its goals. Upcoming experiments conducted using both FLASH and conventional beams will employ the full PET scanner and involve a rich experimental program with novel ideas for irradiation targets, beam characterization, and in-depth comparisons of the two irradiation modalities. Conclusions: This work demonstrates the unprecedented proof-of-principle for the capabilities of an in-beam PET scanner for imaging and dosimetry of both conventional and FLASH proton beams. These results open a new PET modality with proton beams which is particularly attractive for FLASH therapy but can serve effectively all proton irradiations, leading to improved treatment monitoring and image-guided therapy.
Wydawca

Rocznik
Strony
49--54
Opis fizyczny
Bibliogr. 35 poz., rys.
Twórcy
  • University of Texas at Austin, Austin, United States
  • Laboratório de Instrumentação e Física Experimental de Partículas, Coimbra, Portugal
  • Departamento de Física, Universidade de Coimbra, Coimbra, Portugal
  • University of Texas at Austin, Austin, United States
autor
  • University of Texas at Austin, Austin, United States
  • MD Anderson Cancer Center, University of Texas, Houston, United States
  • Laboratório de Instrumentação e Física Experimental de Partículas, Coimbra, Portugal
autor
  • University of Texas at Austin, Austin, United States
  • MD Anderson Cancer Center, University of Texas, Houston, United States
autor
  • University of Texas at Austin, Austin, United States
  • MD Anderson Cancer Center, University of Texas, Houston, United States
autor
  • German Cancer Research Center (DKFZ), Heidelberg, Germany
  • University of Heidelberg, Heidelberg, Germany
  • Hitachi America Ltd, Houston, United States
  • PETsys Electronics, SA, Taguspark, Portugal
autor
  • MD Anderson Cancer Center, University of Texas, Houston, United States
  • MD Anderson Cancer Center, University of Texas, Houston, United States
  • MD Anderson Cancer Center, University of Texas, Houston, United States
autor
  • University of Texas at Austin, Austin, United States
Bibliografia
  • 1. Wilson RR. Radiological use of fast protons. Radiology. 1946;47(5):487-91. doi: https://doi.org/10.1148/47.5.487.
  • 2. Parodi K, Enghardt W, Haberer T. In-beam PET measurements of β+ radioactivity induced by proton beams. Phys Med Biol. 2002;47(1):21-36.
  • 3. Enghardt W, Crespo P, Fiedler F, Hinz R, Parodi K, Pawelke J, et al. Charged hadron tumour therapy monitoring by means of PET. Nucl Instrum Methods Phys Res. 2004;525(1-2):284-8.
  • 4. Crespo P, Shakirin G, Fiedler F, Enghardt W, Wagner A. Direct time-of-flight for quantitative, real-time in-beam PET: a concept and feasibility study. Phys Med Biol. 2007;52(23):6795-811.
  • 5. Zhu X, El Fakhri G. Proton therapy verification with PET imaging. Theranostics. 2013;3(10):731-40. doi: https://doi.org/10.7150/thno.5162.17.
  • 6. Min CH, Zhu X, Winey BA, Grogg K, Testa M, El Fakhri G, et al. Clinical application of in-room positron emission tomography for in vivo treatment monitoring in proton radiation therapy. Int J Radiat Oncol Biol Phys. 2013;86(1):183-9. doi: https://doi.org/10.1016/j.ijrobp.2012.12.010.
  • 7. Seco J, Clasie B, Partridge M. Review on the characteristics of radiation detectors for dosimetry and imaging. Phys Med Biol. 2014;59(20):R303-47. doi: https://doi.org/10.1088/0031-915/59/20/R303.
  • 8. Paganetti H, El Fakhri G. Monitoring proton therapy with PET. Br J Radiol. 2015; 88(1051):20150173. doi: https://doi.org/10.1259/bjr.20150173.
  • 9. Seco J, Spadea MF. Imaging in particle therapy: State of the art and future perspective. Acta Oncologica. 2015;54(9):1254-8.
  • 10. Grogg K, Zhu X, Shih H, Alpert N, El Fakhri G. Proton Range Verification with PET Imaging in Brain and Head and Neck Cancers. J Nucl Med. 2018;59(supplement 1):658.
  • 11. Krishnamoorthy S, Teo BK, Zou W, McDonough J, Karp JS, Surti S. A Proof-of-Concept Study of an In-Situ Partial-Ring Time-of-Flight PET Scanner for Proton Beam Verification. IEEE Trans Radiat Plasma Med Sci. 2021;5(5):694-702.
  • 12. Parodi K, Yamaya T, Moskal P. Experience and new prospects of PET imaging for ion beam therapy monitoring. Z Med Phys. 2023;33(1):22-34.
  • 13. Mryka W, Das M, Beyene EY, Moskal P, Stępien E. Estimating influence of positron range in proton-therapy-beam monitoring with PET. Phys Med Biol. 2023;19(1):96-100.
  • 14. Baran J, Borys D, Brzeziński K, Gajewski J, Silarski M, Chug N, et al. Feasibility of the J-PET to monitor the range of therapeutic proton beams. Phys Med. 2024;118:103301.
  • 15. Favaudon V, Caplier L, Monceau V, Pouzoulet F, Sayarath M, Fouillade C, et al. Ultrahigh Dose-Rate Flash Irradiation Increases the Differential Response Between Normal and Tumor Tissue in Mice. Sci Trans Med. 2014;6(245):245-93. doi: https://doi.org/810.1126/scitranslmed.3008973.
  • 16. Fouillade C, Favaudon V, Vozenin MC, Romeo PH, Bourhis J, Verrelle P, et al. Hopes of high dose-rate radiotherapy. Bull Cancer. 2017;104(4):380-4.
  • 17. Montay-Gruel P, Petersson K, Jaccard M, Boivin G, Germond JF, Petit B, et al. Irradiation in a flash: unique sparing of memory in mice after whole brain irradiation with dose rates above 100Gy/s. Radiother Oncol. 2017;124(3):365-9. doi: https://doi.org/10.1016/j.radonc.2017.05.
  • 18. Vozenin MC, De Fornel P, Petersson K, Favaudon V, Jaccard M, Germond JF, et al. The advantage of FLASH radiotherapy confirmed in mini-pig and cat-cancer patients. Clin Cancer Res. 2019;25(1):35-42.
  • 19. Vozenin MC, Hendry JH, Limoli CL. Biological benefits of ultrahigh dose rate FLASH radiotherapy: sleeping beauty awoken. Clin Oncol (R Coll Radiol). 2019;31(7):407-15.
  • 20. Bourhis J, Montay-Gruel P, Gonçalves Jorge P, Bailat C, Petit B, Ollivier J, et al. Clinical translation of FLASH radiotherapy: why and how? Radiother Oncol. 2019;139:11-7. https://doi.org/doi.org/10.1016/j.radonc.2019.04.
  • 21. Montay-Gruel P, Acharya MM, Petersson K, Alikhani L, Yakkala C, Allen BD, et al. Long term neurocognitive benefits of FLASH radiotherapy driven by reduced reactive oxygen species. Proc Natl Acad Sci U S A. 2019;116(22):10943-51.
  • 22. Hughes JR, Parsons JL. FLASH Radiotherapy: Current Knowledge and Future Insights Using Proton- Beam Therapy. Int J Mol Sci. 2020;21(18):6492. doi: https://doi.org/10.3390/ijms21186492.
  • 23. Fouillade C, Curras-Alonso S, Giuranno L, Quelennec E, Heinrich S, Bonnet- -Boissinot S, et al. FLASH irradiation spares lung progenitor cells and limits the incidence of radio-induced senescence. Clin Cancer Res. 2020;26(6):1497-506. doi: https://doi.org/10.1158/1078-0432.CCR-19-1440.
  • 24. Schuler E, Acharya M, Montay-Gruel P, Loo Jr BW, Vozenin MC, Maxim PG. Ultra-high dose rate electron beams and the FLASH effect: From preclinical evidence to a new radiotherapy paradigm. Med Phys. 2022;49(3):2082-95. doi: https://doi.org/10.1002/mp.15442.
  • 25. Lin B, Gao F, Yang Y, Wu D, Zhang Y, Feng G, et al. FLASH Radiotherapy: History and Future. Front Oncol. 2021;11:644400. doi: https://doi. org/10.3389/fonc.644400.
  • 26. Vozenin MC, Bourhis J, Durante M. Towards clinical translation of FLASH radiotherapy. Nat Rev Clin Oncol. 2022;19:791-803. doi: https://doi.org/10.1038/s41571-022-00697-z.
  • 27. Cesar JP, Kuo A, Morozov A, Ojha A, Jesus B, Leong C, et al. Time-of-Flight PET for Range Verification in Proton Therapy. A poster at the IEEE Nuclear Science Symposium, Medical Imaging Conference, and Room Temperature Semiconductor Detector Conference 2022 (IEEE NSS MIC RTSD 2022). 2022 Nov 5-12; Milano Convention Centre, Milan, Italy.
  • 28. Klein K, Matava W, Layden C, Sadam A, Lang K, Proga M, et al. Time-of-Flight PET for Proton Therapy (TPPT). A poster at the 12th International Conference on Position Sensitive Detectors. 2021 Sep 12-17; University of Birmingham. A poster at the 9th Conference on PET/MR and SPECT/MR and Total-Body PET Workshop, 2022 May 28-June 1; Isola d’Elba, Italy.
  • 29. PETsys Electronics S.A., Taguspark, Ed. Tecnologia I, 24 and 26, 2740-257, Portugal.
  • 30. Titt U, Yang M, Wang X, Iga K, Fredette N, Schueler E, et al. Design and validation of a synchrotron proton beam line for FLASH radiotherapy preclinical research experiments. Med Phys. 2022;49(1):497-509. doi: https://doi.org/10.1002/mp.15370.
  • 31. Yang M, Wang X, Guan F, Titt U, Iga K, Jiang D, et al. Adaptation and dosimetric commissioning of a synchrotron-based proton beamline for FLASH experiments. Phys Med Biol. 2022;67(16):10.1088/1361-6560/ac8269. doi: https://doi.org/10.1088/1361-6560/ac8269.
  • 32. Abouzahr F, Cesar JP, Crespo P, Gajda M, Hu Z, Kaye W, et al. The first PET glimpse of a proton FLASH beam. Phys Med Biol. 2023;68(12). doi: https://doi.org/10.1088/1361-6560/acd29e.
  • 33. Abouzahr F, Cesar JP, Crespo P, Gajda M, Hu Z, Klein K, et al. The first probe of a FLASH proton beam by PET. Phys Med Biol. 2023;68(23). doi: https://doi.org/10.1088/1361-6560/ad0901.
  • 34. Agostinelli S, Allison J, Amako K, Apostolakis J, Araujo H, Arce P, et al. GEANT4 - a simulation toolkit. Nucl Instrum Meth. 2003;506(3):250-303. doi: https://doi.org/10.1016/S0168-9002(03)01368-8.
  • 35. Merlin T, Stute S, Benoit D, Bert J, Carlier T, Comtat C, et al. CASToR: a generic data organization and processing code framework for multi- -modal and multi-dimensional tomographic reconstruction. Phys Med Biol. 2018;63(18):185005
Typ dokumentu
Bibliografia
Identyfikatory
Identyfikator YADDA
bwmeta1.element.baztech-24e42dc3-207c-4001-9ebc-2c32cde759f0
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