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Nanoparticles for enhancing the effectiveness of proton therapy
Pawel Olko Bronowice Cyclotron Centre, Institute of Nuclear Physics PAN, Kraków, Poland
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Methods of cancer treatment
Surgery Chemotherapy Radiation therapy External radiotherapy Brachytherapy Targeted radiotherapy BNCT …….
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Radiotherapy is not always successful
Glioblastoma Pancreatic ductal adenocarcinoma aggressive, frequent recurrence difficulties in diagnosis and treatment enhanced tumour radio-resistance and low radiation tolerance of neighbouring healthy tissu BNCT Clinical studies with C-ions Chiba, Japan Heidelberg, Germany Is it possible to improve effectivness of proton therapy by introducing nanoparticles to target volume?
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Outline Rationale of proton therapy
Physics and microdosimetry of nanoparticles Future work
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Rationale of proton therapy
Dose distribution Verification Low scattered radiation Radiobiology Conformal dose distribution results in saving healthy tissue
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Intensity Modulated Proton Therapy, IMPT
Court. Engelsmann, PSI
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Rationale of proton therapy
Dose distribution Verification Low scattered radiation Radiobiology Verification of range/ dose distribution using the PET/prompt gamma techniques
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Rationale of proton therapy
Dose distribution Verification Low scattered radiation Radiobiology Distant doses from scattered radiation times lower in PT than in classical MV X-rays
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Rationale of proton therapy
Dose distribution Verification Low scattered radiation Radiobiology Protons Belli et al. 2000 Bettega et al. 1979 Relative Biological Effectivness increases for low energy protons
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Proton therapy – low LET radiation?
BEAM BEAM Say the same configuration as before Nuclear reactions -> secondaries Explain LET method Secondary ions Protons L. Grzanka, NEUDOS-13, 2017
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Can we locally increase energy deposition?
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Boron Neutron Capture Therapy
10B + nth → [11B] *→ α + 7Li MeV Ea = 1.47 MeV , Range ~ 9 um, LET~ 190 keV/um
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Photon interactions with high Z elements – photoelectric effect
Mass energy absorption coefficent for gold (Z=79)
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Dose enhancement for orthovoltage X-rays on high-Z elements
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Nanoparticles Particles: 1-100 nm
Large surface as compared to total amount Mainly Ni, Fe, Au, Pt M. Parlińska, IFJ PAN
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Nanoparticles Particles: 1-100 nm
Large surface as compared to total amount Mainly Ni, Fe, Au, Pt M. Parlińska, IFJ PAN
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Enhanced proton treatment in mouse tumors through
proton irradiated nanoradiator effects on metallic nanoparticles Jong-Ki Kim et al., Phys. Med. Biol. 57 (2012) 8309–8323
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Enhanced effectiveness of protons + nanoparticles
Jong Ki Kim 2012 Phys Med. Biol. 57
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Mechanism of dose amplification by gold nanoparticles, AuNP
Jong Ki Kim 2012 Phys Med. Biol. 57
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Mechanism of dose amplification by gold nanoparticles, AuNP
Jong Ki Kim 2012 Phys Med. Biol. 57
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Microdosimetry of low-energy photons
P.Olko, Ph.D. thesis 1989 Low energy photons can enhanced RBE because of short, densely ionizing electron tracks
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Spatial distribution of nanoparticles in biological cells
- how does it influence the proton action Yuting Lin et al 2015 Phys. Med. Biol
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Irradiation modalities: protons, MV X-rays and kV X-rays
Yuting Lin et al 2015 Phys. Med. Biol
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Local doses in the vicinity of gold nanoparticles (GNP)
Yuting Lin et al 2015 Phys. Med. Biol 50 nm GNP protons For lower GNP diameters dose increases close to the surface
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Cell survival after proton irradiation with gold nanoparticles (GNP)
Yuting Lin et al 2015 Phys. Med. Biol For the same weight the smallest GNPs are more effective
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Cell survival after irradiation with gold nanoparticles (GNP)
Yuting Lin et al 2015 Phys. Med. Biol If NPs are not introduced in cell nucleus – no effect on survival
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Survival for protons, 6 MV X-rays,250 kVp X-rays
Yuting Lin et al 2015 Phys. Med. Biol Protons and MV X-rays show equivalent survival only when the GNPs are in cell nucleus
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Future work 1) New biofunctionalised NP 2) Cell radiobiology with NP
3) Radiobiology in animal models 4) Imaging NP transport with MRI 5) Microdosimetry of NP 6) TPS with included NP. modules
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Future work 1) New biofunctionalised NP 2) Cell radiobiology with NP
3) Radiobiology in animal models 4) Imaging NP transport with MRI 5) Microdosimetry of NP 6) TPS with included NP. modules Uptake kinetic of the gadolinium based contrast agent in model tumour as assessed by 9.4T DCE MRI study at IFJ PAN [11].
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Future work 1) New biofunctionalised NP 2) Cell radiobiology with NP
3) Radiobiology in animal models 4) Imaging NP transport with MRI 5) Microdosimetry of NP 6) TPS with included NP modules Alpha-particle and 3H tracks observed in LiF FNTD developed at IFJ PAN (Bilski & Marczewska, 2017
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Future work 1) New biofunctionalised NP 2) Cell radiobiology with NP
3) Radiobiology in animal models 4) Imaging NP transport with MRI 5) Microdosimetry of NP 6) TPS with included NP modules TPS with option for calculation of enhanced RBE/dose due to proton interaction with NP
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M. Lekka, M. Parlińska, MPR Waligórski, W. Weglarz
Thank you Acknowledgements to: M. Lekka, M. Parlińska, MPR Waligórski, W. Weglarz
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