Haddad F. Subatech/ ARRONAXasso-lard.eu/wp-content/uploads/2010/08/LARD.pdf · Target holders We...
Transcript of Haddad F. Subatech/ ARRONAXasso-lard.eu/wp-content/uploads/2010/08/LARD.pdf · Target holders We...
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Production de radionucléides et recherche sur
les cibles
Haddad F.
Subatech/ ARRONAX
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CreditsARRONAX :C.Alliot, A.C. Bonraisin, V.Bossé, C.Bourdeau, S. Girault, C. Huet, F. Haddad,
J.Laizé, E.Macé, N. Michel, M. Mokili, L.Perrigaud, C. Roustan, N. Varmenot
Bureau d’étude mecanique (Subatech) : Olga Batrak, Jean Michel
Buhour, Arnaud Cadiou, Gérard Guilloux, Mériadeg Guillamet, Gilles
Bouvet
Atelier mécanique (Subatech): Sylvain Fresneau, Yann Bortoli, Thierry
Milletto
CEMHTI (Orléans): Isidro Da Silva and the cyclotron team
Théranean: AAA, Arronax, Cerma, INSA, INSERM, nano-h, ULB,
Subatech
Alpha-RIT: Atlab-Pharma, ARRONAX, Chelatech,IBA,INSERM,
Subatech
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Lignes
de
production
Connecté par un système
pneumatique aux cellules
blindées
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Irradiation station
cross section
Hall P2, P3, A1 and A2
Rabbit
Collimator
F 10mm ou 20mm
target
Water
inlet
Water
outlet
Keep the external
shape and connections
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Target holders
We need to irradiate solid target under different forms (powder, foils,…).
Two target designs will be available (medium beam current )
• A 15° rabbit (delivered by IBA – co-design by SUBATECH)
• A multi target rabbit Water outletWater inlet
Beam
target
Cross section
of the 15° rabbit
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Multi-target system
Encapsulated material with flowing water around
Multi-cibles1
2
Encapsulation
(soudage laser)
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Démontage navette
Processing in hot cells
Extraction/purification
Distribution
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Radiothérapie interne vectorisée:211At : appropriate for a-therapy due to its half-life (7.2 hours).
67Cu et 47Sc : b-therapie (même energie b)
Nécessite l’utilisation de protons de haute énergie et
des courants faisceaux élevés (les sections efficaces de
production (p,2p) sont faibles)
Imagerie PET:64Cu et 44Sc: dosimétrie PET pré-thérapeutique avant injection
des émetteurs b- 67Cu et 47Sc
82Sr/82Rb et 68Ge/68Ga générateurs
44Sc: b+ g émetteur (imagerie 3 g)
Notre liste de priorité
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99Tc-MIBI
SPECT
82Rb-TEPD. Le Guludec et al, Eur J
Nucl Med Mol Imaging
2008; 35: 1709-24
Principaux avantages de TEP/SPECT
1- Durée d’examen plus court (2 à 5 hrs vs 45 min)
2- Spécificité supérieure (femmes et surpoids) (artéfacts d’atténuation non uniforme de SPECT)
3- Quantification possible (atteinte tri-tronculaire)
4- Dose patient 2 à 3 fois plus faible
Générateurs Sr-82/Rb-82 - Cardiologie
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Sr82
Rb82
Kr82
(stable)
T1/2=75sT1/2=25.5 j
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Production du 82Sr
RbCl (en cours)
ou
Rb métal (collab.
INR)
Cible:
•Pastilles encapsulées de RbCl
•Dual target
0.16mCi/µA/h
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Extraction and separation of 82Sr
DissolutionPastille RbCl irradi é e
Chel
ex1
00
82 Sr
82Rb,
83Rb,
83mRb,
84Rb,
86Rb
82Sr,
85Sr,
32P,
83mKr…
Rb, P, …
R é sine de s é paration
Purification de Sr
Irradiation dans un
Cyclotron de la
pastille de RbCl
85 Rb(p,4n) 82 Sr
Purification de Sr
Reproducibility verified
yield = 92.9 % 3.7% (k=2)
1er lot test envoyé le 15/10/2010 – 40 mCi
1,00E-04
2,00E+04
4,00E+04
6,00E+04
8,00E+04
1,00E+05
1,20E+05
1,40E+05
1,60E+05
0 50 100 150 200
V elution (mL)
Activ
ité (B
q)
Zone
d'élution
Sr
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64Cu– Imagerie TEP
T1/2 = 12,7 h
Collaboration:
ARRONAX – Subatech -CEMHTI
17,6% 43,9%
38,5%
Cible de Ni-64 (enrichie
98.8% ) sur un support en
Or obtenue par
électrodéposition
64Ni + p 64Cu + nProduction: Gamme en énergie
12-10 MeV
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Extraction et séparation chimique
Principaux contaminants:
•61 Co obtenu par (p,a) mais aussi des traces d’autres isotopes
de cobalt (55 Co, 56 Co, 57 Co ).
•Nécessité de récupérer le 64Ni ( ~20 € / mg)
Principe de l’extraction/séparation: dissolution dans HNO3 puis
utilisation d’une colonne AG1x8.
Irradiation au CEMHTI
(Orléans)
Pureté radionucléidique
> 99,8 %
Récupération 64Ni > 90%
Projet collaboratif Cu-ATSM pour l’hypoxie
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Générateurs
Ge-68/Ga-68
Utilisation avec des
molécules ayant
une bio-cinétique
rapide:
Peptides, fragment
d’anticorps,…
E(g)= 1077,34 (3,22
%)
68Ge– 271,95 j
68Zn - stable
CE 100%
68Ga – 67,71 mnb+ 89,14%
CE 10,96%
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La gamme en énergie est complémentaire de celle utilisée pour produire le 82Sr.
Mise en place d’une « dual Target » permettant l’irradiation simultanée de
Strontium-82 et de Germanium-68:
Les rendements de production étant faible (0,06 mCi/µA/h), on doit travailler à
haute intensité pour avoir un coût de revient raisonnable:
Gamme en énergie
15 - 30 MeV
69Ga + p 68Ge + 2n
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Astate-211
E(g)= 569,7(97,8 %)
E (g)=1063,7 (74,6%)
E(g)= 1770,2 (6,9 %)
211At– 7,2h
207Bi – 32,9a
207Pb - stable
a
41,8%
e
58,2%
CE
100%
211Po – 0,516sa
100%
At210At211
Voie de production:
209Bi + a 211At + 2n
Gamme d’énergie:
[ 20 MeV - 28,3 MeV]
Production attendue sur ARRONAX: 0,7 mCi/µA/h ( 210At/211At <10-5 )
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Mise en place de la chaine de production:
cible ARRONAX – irradiation CEMHTI – extraction INSERM
production 200MBq (EOB) – extraction voie sèche 80% - récupération 80 MBq
Bi 25-40 µm
Cible solide obtenue par evaporation
sous vide sur support AlN
Extraction par voie sèche:
ice
600°C
Alpha-RIT: Radio Imuno-Therapy using 211At
major indication: prostate cancer
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19
Reflector/
moderator
Cooling/moderator
19
neutrons
TargetPROTON BEAM
CYCLOTRON
Activation samples
A proton beam is generated by a
cyclotron
Protons interact with a solid target
(Be)
Fast (high energy) neutrons are
generated
Neutrons are moderated (water)
Neutrons are reflected and further
moderated (graphite)
Nanoparticles are activated by
moderated neutrons
THERANEAN project: Therapy through Neutron
Activation using Nanoparticles
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The THERANEAN method
GRAPHITE
REFLECTOR
LEAD
BUFFER
IRRADIATION
CAVITY
WATER
MODERATOR
AND COOLING
TARGET
PROTON BEAM
Cooling/
moderator
Reflector
Target
Activation channel
neutrons
Transf er o f im aging d at a t o
Mont e-Car lo d osim et ry m od el
f o r d ose d ist r ib ut ion calcu lat ion
Synt hesis o f var ious t yp es and sizes o f
nanop ar t icles w it h lan t han id e-oxid e co re,
con t ain ing t he st ab le (non rad ioact ive) iso t op e t o
b e act ivat ed
In t ra-t um oral/in t ra-ar t er ial in ject ion using t he
TMT in ject o r
SPECT d et ect ion o f nanop ar t icles d ist r ib ut ion ,
CT f o r m orp ho logical d at a
Pharm aceut ical p rep arat ion o f
st er ile in ject ab le nanop ar t icles
susp ension Inser t ion o f in ject ab le d oses in t he
cyclo t ron -d r iven act ivat o r f o r neut ron
act ivat ion (no alt erat ion o f p harm aceut ical
charact er ist ics)
Courtesy of NanoHCourtesy of NanoH
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ConclusionsARRONAX est maintenant opérationnel
La production de strontium a débuté (sept/oct 2010)
Production de Cuivre-64 est prévue fin 2010
Production d’Astate-211 est prévue avril 2011
Plusieurs projets collaboratifs ont débuté :
– Theranean: activation of nanoparticle for brachytherapy
– Alpha-RIT: alpha immunotherapy using 211At
– Cu-ATSM pour l’hypoxie
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Merci pour votre attention
ARRONAX a été construit grâce à l’aide:
Du Conseil régional des Pays de la Loire
De l’Université de Nantes
Du gouvernement français (CNRS, INSERM)
De l’union européenne