Arthur BONGRAND Séminaire de Radiothérapie Interne Vectorisée - Archive ouverte HAL

Séminaire de Radiothérapie Interne Vectorisée
 Arthur BONGRAND
 Samuel DUVAL, Arnaud GUERTIN & Julie CHAMPION

 Projet BePAT :
BeaQuant, un autoradiographe numérique au service de la production de
 radionucléides pour des applications en médecine nucléaire
 15/03/2022

2

 Physics of Radiations InteractionS with Matter and Applications

 RaMI IRMa HB
RaMI → Radionucléides Médicaux Innovants – Innovative Medical Radionuclides
 ✓ Health Cross section measurement
 ✓ Nuclear medicine → Isotope productions
 ✓ Radionuclides Masse separation and laser ionisation: SMILES ☺

IRMa → Interaction Rayonnement Matière – Radiation-Matter Interaction
 ✓ Ion Beam Analysis, materials → IBA platform: visible, X, 
 ✓ Non Destructive Testing → Nuclear data X, : PIXE/PIGE - High Resolution X-Ray Tomography System
 ✓ Detector development and characterization → profilers, diamond detectors, dosimeters…

HB → HadronBiologie – HadronBiology
 ✓ Health, Radiobiology, Dosimetry, Flash Hadrontherapy → In-situ dose monitoring &
 Arthur BONGRAND Irradiation platform: proton and 15/03/2022
 α beams

3

 Most important factors
 →Purity & Quantity
 Extraction
 Need identified
 &
 in the clinic: Determine High current Purification
 Advances in biology, the optimal
 oncology ... production path Chemistry/Physics

 Identify the (best) Develop Towards
 candidate targeting preclinical use
 Nuclear data
 radionuclides Fundamental chemistry
 Cross section
 Radiochemistry
 Range of energies Highest beam
Extracted particles
 (MeV) intensity (µA)
 BePAT
 H+ (protons) 35 – 70 375 x 2
 How autoradiography can be useful in the acquisition
 He2+ (alpha) 68 70
 of nuclear data for the production of radionuclides for
 HH+ 35 50
 nuclear medicine applications ?
 D+ (deuteron) 15 – 35 50

 Arthur BONGRAND 15/03/2022

4

• Autoradiography
 → An emission imaging technique carried out from a radioactive
 source placed in contact with an emulsion, a photographic film or an
 adapted detector
 Glass slide
 → Area of interest located at the surface (≈ 10 µm deep)
• Applications
 Th
 → Pre-clinical (oncology + drug discovery)
 Visualization of molecules or fragments of molecules a “sugar”
 labeled with radioactive elements Metal foil
 Lefeuvre et al., under review NIMA
 → Geology (study of uraniferous rocks, environmental pollution...)
• Samples BeaQuant
 → "Thin" (

5

 Sectional view
Ne(90%)CO2(10%) at 1bar Laboratoire Imagerie et Cerveau, Unité Inserm
 Copper scotch Sample 930 Université François-Rabelais de Tours

 Glass slide
 Insulating Insulating
 material Amplification space 1 material

 Electron trajectory
 Micromesh 1 In vivo rat brain labelled with LBT999 - 18F
 18F Spatial resolution: 50 µm
 
 Drift space
 Electronic UCB
 cloud

 Micromesh 2 1 cm

 Amplification space 2 125I
 QWBA
 Spatial resolution: 50 µm
 Pixelated reading floor

 Arthur BONGRAND 15/03/2022

6

 Sectional view
Ne(90%)CO2(10%) at 1bar Sample *
 +metallization
 Glass slide
 Conductor material Conductor material

 Insulating Amplification space 1 Insulating
 material material
 0 mm 20 mm

 Alpha trajectory Electronic Isotope: 226Ra
 Micromesh 1
 cloud Spatial resolution : 20 µm
 *
 Drift space

 Micromesh 2

 0 mm 25 mm
 Amplification space 2
 Pixelated reading floor Uranium ore sample (238U,235U,234U)
 Spatial resolution: 20 µm
 Arthur BONGRAND
 * Lefeuvre et al., under 15/03/2022
 review NIMA

7

 • Samples
 Ti
 → Metal foil BeaQuant
 → Metal foil electrodeposited
 after digestion and chemical separation (in the future)
 Th Al

 • Sample activity
 Capsule and metal foils → Insensitive to γ and X
 → A(α) + A(β+) + A(β-) < 20 kBq Specific calculations required !

 • Challenge
 → Short-lived isotope !

Metal foil can be electrodeposited
after digestion and chemical
separation

 Arthur BONGRAND 15/03/2022

8
 • α therapy benefit
 230Pa • Short range in human tissues : ≈ 100µm (≈ cell diameter)
 Goal : • High Linear Energy Transfer (LET) : 60-200 keV/µm
 • Great DNA damages → no cell repair

 • 230U/226Th from 230Pa
 considering Arronax’s characteristics
 17 and 30-70 MeV Proton beam

 Th-232(p,3n)Pa-230
Protons

 « Stacked foil » experiment

 α:
 Ti 28.3
 MeV

 Moulin, 2021
 Th Al Chemical separations of Pa-230 and U-230
 after production
 → Contaminant :
Irradiation station and beam line Capsule and foils −
 1/2 : 27j, β )
 233Pa (t

 1/2 : 104 ans, α ≈ 5MeV)
 Arthur BONGRAND 231Pa (t 15/03/2022

9

 Goal : 230Pa
 Arronax 17, 30-70 MeV
 230U/226Th from 230Pa

 α:
 28.3
Protons Th-232 MeV
 Th-232(p,f) Duchemin, 2015
 tel-01220522
 « Stacked-foil » experiment
 • Contaminant
 233Pa (t1/2 : 27j, β−)
 1/2 : 104 ans, α ≈ 5MeV)
 Ti 231Pa (t

 • In a nutshell
 → Large number of fission products
 Th Al
 not detected by γ spectroscopy
 → Need for α spectrometry !
Irradiation station and beam line Capsule and foils
 Arthur BONGRAND → BePAT ! ← 15/03/2022

10

 X Available
 X Not available

03/2022

 Z>83 : there remains the "grey" market: the stock of other laboratories…

 The law is hard, but it's the law (Dura lex, sed lex)

 Arthur BONGRAND 15/03/2022
 03/2022

11

 Aim of BePAT: to work on the development of spectrometry with metal foil
 Production of α elements from 210Bi ! Study of a theranostic pair:
 metallic 211At, 211Po ! (187Ir ,189Ir)

 ▪ α-emitter (5.9 MeV and 7.45 MeV) ▪ “Strike” Auger *
 ▪ Can be produced "easily" @Arronax Targets DNA or important structural units 1-100nm
 cell nucleus and other organelles 1-10μm
 ▪ Well-known element
 but ▪ β+/Auger pair produced at the same time
 Ideal to optimize α spectroscopy method with a natural rhenium metal foil & α beam

 ▪ Good chemical characteristics but many
 Ti
 contaminants 188-190Ir

 ▪ Exploratory work

 ▪ Gamma spectroscopy methods
 Bi Al
 can be used !

Irradiation station and beam line Capsule and foils ▪ Ø α produced
 Arthur BONGRAND * Filosofov et al., 2020 DOI: 10.1016/j.nucmedbio.2020.12.001
 15/03/2022

12

Goal : Search for the energy deposit in the gas to get the initial kinetic energy of the α particle
 Simulation Monte-Carlo:

→ Understanding the signals induced by the α
→ Characterization of the detector
→ Simulation of a localized α-spectroscopy using
 Garfield++ (CERN) in Geant4

 Arthur BONGRAND 15/03/2022

13

Lefeuvre et al., under review NIMA

 226Ra α 4784 keV (96%)

 INFN Torino TIGER design group

 Arthur BONGRAND 15/03/2022

14

 BePAT’s goal: BeaQuant
Demonstrate how autoradiography can be useful in the acquisition of nuclear data
for the production of radionuclides for nuclear medicine applications !

 → To work on the development of spectrometry with metal foil

 → Localized spectrometry

 → Supported by the simulation

 prisma@subatech.in2p3.fr samuel.duval@ai4r.com
 Arthur BONGRAND www.ai4r.com

15

Arthur BONGRAND 15/03/2022

Collaborations: à l’échelle locale : GIP Arronax, Ceisam, Ai4R; à l’échelle nationale IJC Lab, pHLAM, et à l’échelle
internationnale: INR.

Financements: TransForMed (Next), PRC Franco-Russe (PaTH project , 2020-2022), ANR CHESS (2022-2026),
Plan de relance (2021-2023), Labex IRON2 (2020-2024).

 julie.champion@subatech.in2p3.fr

 16