BIOphysical characterization of Helium and Oxygen ion beams for hadronTherapy - Proposta di nuovo esperimento
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BIOphysical characterization of Helium and
Oxygen ion beams for hadronTherapy
Proposta di nuovo esperimento
INFN-CSNV
2023-25
Participating units Scientific motivation Objectives Tentative budget
BIOHOT composition
• NA/LNS, PV, Roma TRE
– RN L. Manti (NA)
– ROMA TRE: A.Antoccia 0.8 FTE, F.Berardinelli 0.4 FTE, A.Sgura 0
.1 FTE + V. Dini (Roma 1-INFN) 0.1 FTE = 1.4 FTE
– 6.6 FTE Totali
• Partners
– CNAO (Centro Nazionale di Adroterapia Oncologica)
– HIT (Heidelberg Ion-beam Therapy centre)
– Queen’s University, Belfast, UK
Scientific motivation-1
• Hadrontherapy (HT) currently exploits proton and 12C-ion
beams
• New ions are of interest for possible clinical advantages
• 4He is superior to protons due to less lateral scattering
and range straggling and slightly higher LET
– Higher dose conformity to tumour with greater RBE
– Reduced dose to surrounding tissues
– Indications for paediatric and/or close-to-OAR radioresistant
tumours
• At HIT, 4He HT is at an advanced stage (first patient
treated)
• CNAO will have a new source accelerating 4He beams by
2023
Scientific motivation-1
• 16O is more biologically effective than 12C ions
– Potential benefit against hypoxia- and defective DNA damage
repair-based radioresistance over basically all the SOBP
– Greater insensitivity to cell-cycle variations
– Enhanced anti-angiogenic and anti-metastatic properties
• Both HIT and CNAO are also considering clinical use of 16O
beams
BIOHOT objectives
ØDespite the HIT experience, in vitro and in silico pre-clinical
data are still much needed for 4He and 16O. Hence we aim at:
Fully characterizing these new HT beams through an integrated
biophysical approach
– Experimental radiobiology using endpoints for tumour control and
normal-tissue complications (NA; RM3)
– Modellization and MC-based simulations (PV; LNS)
– Microdosimetric measurements (LNS)
• This will prove essential also for facility intercomparison
between HIT and CNAO
Budget • Financial requests will be in line with those of normal experiments, tentatively between 20 and 40 k€ per Unit per year • Thus, if funded, the budget may be around 90 k€ for 2023
RM3 • Parametri Radiobiologici valutati per radiazioni di riferimento (RX), ioni 4He e 16O • Linee Cellulari: Tumorali: Saos-2 (osteosarcoma), PANC-1 (pancreas) • Tessuto Sano: fibroblasti normali MRC-5 • Sistemi cellulari 2D e 3D - In collaborazione con Belfast: Effetto Ossigeno 1) Saggi clonogenici per la sopravvivenza 2) Cinetica di riparazione DSBs 3 ) Caratterizazione del danno cromosomico (mFISH )
Struttura della traccia e Lesioni al DNA
Le RI depositano l’ energia in modo
diversoRelazione tra LET e RBE L’ Efficienza Biologica Relativa (RBE) è il rapporto tra un certo effetto biologico generato da una dose di radiazioni a basso LET (radiazione di riferimento e l’ effetto della radiazione da testare.
Saggi Clonogenici in Cellule Tumorali
Cell line 1 Cell line 2
Dose (Gy)gH2AX Focus Formation
• H2AX is phosphorylated at the site of DNA DSBs
• Antibody to phosphorylated gH2AX reveals foci, the number of which
approximates to the number of DSB.
• DNA repair proteins are recruited to the same foci.
• gH2AX foci are apparent within a minute; reach a max in 10 min.
Dephosphorylation starts after 30 minutes with a t1/2 of about 2 hr
• The rate of repair and residual damage can be assessed within 24hrs
0Gy 1Gy 2hr 1Gy 24hr
uuytityStruttura di traccia e DSBs nelle cellule Rogakou et al 1998
CINETICA DI RIPARAZIONE DELLE DSBs
Aberrazioni Cromosomiche
Radio-indotteLa Multicolor FISH (M-FISH)
Multicolor FISH Traslocazione 3 -9
La M-FISH evidenzia Traslocazioni compl
esse prodotte da Radiazioni densamente
ionizzanti (Protoni a bassa energia, ioni
elio, ioni carbonio)
Traslocazioni Complesse
Berardinelli et al. 2015
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