Production of non-conventional high
specific activity radionuclides for
biomedical, toxicological and
environmental purposes
Flavia Groppi, Mauro Bonardi, Luigi Gini
Dipartimento di Fisica – UNIMI and INFN Sezione di Milano
L.A.S.A. Via F.lli Cervi, 201 20090 Segrate (MI)
Enzo Menapace
Divisione per le Tecnologie Fisiche Avanzate – ENEA, Bologna
Zeev Alfassi
Department of Nuclear Engineering, Ben Gurion University, Be’er Sheva , Israel
Boris Zhuikov
Institute for Nuclear Research of Russian Academy of Sciences, Moscow, Russia
Kamel Abbas, Uwe Holzwarth, Neil Gibson
Institute for Health and Consumer Protection, JRC, EC, Ispra (Va)
13 October 2005
[email protected]
Highligths_Physics
[email protected]
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Main Research Fields
• Studies of non-conventional high specific activity
radionuclides by Cyclotron and Nuclear Reactor
• Quality Control of radiopharmaceutical compounds
labelled with short- lived and high specific activity
radionuclides: by ,  and  spectrometries, atomic
absorption spectrometry, liquid scintillation counting,
radioichromatography
• Accelerator Driven Systems for Transmutation of
Nuclear Wastes
• Determination of actinoids (U, Th, Np, Pu, Am, DU) in
biological and environmental matrices, ,  and 
spectrometries
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Main uses of
No Carrier Added Radiotracers
some NCA
radiotracers
applications
metallobiochemistry
environmental
toxicology
nuclear medicine
behaviour
of different chemical
forms of
trace elements
Low Level and
Long Term
Exposure (LLE)
to ultra-trace elements
radiodiagnostics
(SPECT, PET)
systemic radionuclide
tumour therapy
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Production of a N.C.A. radionuclide
MAIN STEPS
Nuclear Reaction
Studies
N.C.A.
radiochemical
processing
Quality
Control
thin-target
excitation functions
Ultra-high
purity chemicals
Radionuclidic
Purity
thick-target
yields
Ultra-high
purity targets
Radiochemical
Purity
irradiation conditions
optimisation
ultra-high
purity equipments
Specific
Activity
Radionuclidic
Purity
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N.C.A.
Labelled
compound
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Chemical
Purity
4
Origins of Isotopic Carrier
(both stable and radioactive)
preparation
pit falls
in NCA
radiotracer
target material
and target holder
side
chemical impurities
nuclear reactions
in target radiochemical
processing
very common
in cyclotron
irradiation
use of glassware
instead of
inert materials
(i.e: teflon-PFA)
impurities
in practice
"not avoidable"
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Recent Projects co-funded by INFN
 RAME-64 (2001-2002): study of cyclotron production,
radiochemical separation and QC of high specific
activity copper-64 (copper-61) by deuteron irradiation
on natural Zn target
 ASTATO (2003-2005): study of cyclotron production
of astatine-211 (internally spiked by astatine-210) by
alpha irradiation on Bi target. Radiochemical separation
and QC. Targetry improvement. Polonium-210
dosimetry !
 RENIO (2006–2007): study of cyclotron production of
rhenium-186g by proton or deuteron irradiation on W186 target. Radiochemical separation and QC.
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Nuclear reactions, main nuclear data and applications of radioisotopes
used in nuclear medicine under study
Radionuclide
T1/2
reactions
gamma emissions
imaging
radiotherapy
64Cu
12.70 h
natZn
(d,X)
 511 keV
PET
+ and -
61Cu
3.33 h
natZn
(d,X)
 511 keV
PET
impurity
66Ga
9.49 h
natZn
(d,xn)
 511 keV
many gammas
PET
-camera
+ , 4.2 MeV
(p,n)
186W (d,2n)
 137 keV
other gammas
SPET
-camera
- , 1.1 MeV
186W
186gRe
89.25 h
211At

211Po 
7.22 h
516 ms
209Bi
(,2n)
X 79 keV
-camera
 , 5.868 MeV
 , 7.448 MeV
210At

210Po 
8.3 h
138.4 d
209Bi
(,3n)
many gammas
-camera
internal spike
 , 5.304 MeV

213Bi 
213Po 
10.0 d
45.6 m
4.2 ms
226Ra
(p,2n)
many gammas
SPET
-camera
, 5.829 MeV, others
- , 1.4 MeV
 , 8.375 MeV
103Pd
16.97 d
103Rh
(d,2n)
X 20,22,23 keV
some gammas
---
X 20, 22, 23 keV
225Ac
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211At
direct methods
Bombarding Bi metallic
targets with light ions
209Bi(t,
209Bi(,
production methods
JRC-Euratom Ispra cyclotron
K = 38
Tmax/A = K (Z/A)2
n)211At
I up to 60 mA
2n)211At
indirect methods
d up to 19 MeV
p ,  up to 38 MeV
Beam line
Irradiation chamber
From the decay of its
precursor 211Rn
209Bi(6Li,
4n) 211Rn  211At
232Th(p, spall) 211Rn  211At
232Th(, spall) 211Rn  211At
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Decay scheme of 211At
211mPo
211At
25,2 s
211gPo
e 99,825
%
207Pb
stabile
ES(MeV)
T1/2
209Bi(,2n)211At
20,72
7,214 h
209Bi(,3n)210At
28,61
8,1 h
23,76
138,376 d
15,11
138,376 d
21,49
138,376 d
2n)210Po
209Bi(,t)210Po
13 October 2005
n)210Po
138,376 d
 0,175
%
(on 206Bi)
E=5,3 MeV
Reaction
209Bi(,d
210Po
516 ms
 100 %
(on 206Pb)
 100 %
E=7.5 MeV
e 100 %
8,1
h
t
e 58,2 %
31,55 a
209Bi(,p
210A
7.214 h
 41,8 %
E=5.9 MeV
207Bi
Decay scheme of 210At
The energy of the alpha particles range from
4992 keV to 7451 keV with an “average “ value
of 6.22 MeV.
The  particles of the 211At/211gPo have an
“average” range of 60 mm in water (and soft
animal tissues), and a nearly optimal LET of
130 eV·nm-1, which is around the maximum of
Q curve for energetic ions.
The 207Bi is produced in negligible ammount.
The atatine is an alogen: chemistry for
labelling molecules is similar to that for iodine.
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•Radiochemical separations
•Nuclear measurements (, ,  spectrometry)
1. Dissoluzione del
target irraggiato
Dissoluzione del Bi in HNO3
concentrato
Aggiunta alla soluzione
di HCl 8 M
2.Estrazione
liquido/liquido
Estrazione in solvente organico
etere diisopropilico (o tetracloruro di carbonio)
Fase organica
astato-210,211
Lavaggio con HCl 8
M
3. Ri-estrazione in fase
acquosa
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Resa:
98 %
Fase acquosa
polonio-210 e Bi
Ri-estrazione con
etere diisopropilico
Riduzione in forma anionica dell’astato con agente riducente
(cloruro di idrossilammonio)
Resa:
50 %
In alternativa riduzione in forma anionica dell’astato in
soluzione basica (NaOH)
Resa:
90 %
10
HPGe  spectrum – 28.8 MeV irradiation
zoom region
211
At/
211g
79.3 keV
Po
7
10
89.6 keV
7
10
6
10
211
At/
counts
76.9 keV
211g
Po
6
10
569.702
211
At
5
counts
10
92.4 keV
687.00
211
At/
211g
Po
897.80
210
At
245.31
4
5
10
10
50
210
60
At
207
Bi
3
10
211
At/
2
1063.67
211g
70
80
90
100
gamma energy (keV)
1181.4 1436.7
1483.6 1599.7
Po
328.12
207
10
Bi
211
At
1770.23
669.60
742.64
1
10
500
1000
1500
2000
gamma energy (keV)
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110
7000
8000
7450.6 keV
Po (t1/2= 516 msec)
211g
60
5304.4 keV
5000
6000
7000
8000
alpha energy (keV)
alpha energy (keV)
alpha spectrum after the liquid/liquid extraction: the
peaks of both 211At-211gPo and 210Po are shown
together (related to 32.8 MeV irradiation).
polonium fraction
in aqueous phase
alpha spectrum of the astatine fraction (extracted by
the organic solvent): At product is completely
extracted from the aqueous solution.
210
Po (t1/2= 138.376 d)
-1
kcounts x channels
90
5867.7 keV
120
0
6000
120
80
At (t1/2= 7.214 h)
150
211
211g
211
180
30
0
5000
100
astatine fraction
in organic phase
-1
210
210
200
5304.4 keV
400
Po (t1/2= 138.376 d)
600
5867.7 keV
At (t1/2= 7.214 h)
-1
counts x channels
800
240
kcounts x channels
after L/L exstraction
1000
7450.6 keV
Po (t1/2= 516 msec)
1200
60
40
alpha spectrum of the separated 210Po fraction
(remained in the aqueous phase): none of the 210Po is
taken into the organic solvent extraction.
20
0
5000
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6000
7000
alpha energy (keV)
8000
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12
1600
800
600
400
200
0
1400
210At
Kelly-Segrè 1949 (I)
Kelly-Segrè 1949 (II)
Kelly-Segrè 1949 (III)
Ramler 1959
Stickler et al. 1974
Lambrecht-Mirzadeh 1985
Rattan et al. 1986
Rizvi-Bhardway 1990
Singh-Mukherjee 1994
Patel-Shah-Singh 1999
Fit dati letteratura
Dati simulati (EMPIRE-II)
Fit dati simulati
1200
sezione d'urto (mb)
sezione d'urto (mb)
Kelly-Segrè 1948(I)
Kelly-Segrè 1948 (II)
Kelly-Segrè 1948 (III)
Ramler 1958
Lambrecht-Mirzadeh 1985
Fit dati letteratura
Dati simulati (EMPIRE-II)
Fit dati simulati
211At
1000
1000
800
600
400
200
0
20
25
30
35
30
40
energia incidente particelle alfa (MeV)
E(MeV)
TTY (GBq/C)
35
40
45
50
55
60
65
TTY (GBq/C)
E(MeV)
18
24
209Bi(,
22
20
70
energia incidente particelle alfa (MeV)
2n)211At
14
13
209Bi(,
15
6
5.5
5
3n)210At
4.5
12
4
16
11
3.5
14
10
12
9
10
8
18
12
3
9
2.5
2
6
8
1.5
7
6
5
4
2
3
0
1
20
24
28
32
36
energia incidente particelle alfa (MeV)
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2005
1
3
0.5
0
29
40
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30
31
32
33
34
35
36
37
38
energia incidente particelle alfa (MeV)
39
40
13
Production of 186Re via (p,n) reaction on 186W target
140
Empire II
Szelecsenyi et al. (1997)
Shigeta et al.(1996)
Zhang et al 1999
2
-27
cross section (cm x 10 )
120
100
80
60
40
20
0
10
20
30
proton incident energy (MeV)
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Nuclear Physics Laboratory:



4 HPGe connected to 4 MCAs
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Nuclear Physics Laboratory:
NaI(Tl),  spectrometer, Geiger-Müller
13 October 2005



Liquid Scintillation Counting
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Cold Chemistry Laboratory for trace analysis
UV-VIS spectrophotometry, polarography-SV, ET-AAS
radio-TLC, radio-PC
radio-HPLC, radio-GC
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Warm Radiochemistry Laboratory: Class II
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Warm Radiochemistry Laboratory: Class II
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Hot Radiochemistry Laboratory: Class II
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Main Collaboarations with
Research Centres
• Institute for Health and Consumer Protection, JRCIspra, CE, Varese
• Centro Radiochimica/Spettroscopia, CNR, Pavia
• ENEA- Centri di Bologna, Saluggia
• Dipartimento Scienze Ambientali e Scienze Materiali,
Milano-Bicocca
• Intitute for Nuclear Research, INR, Troitsk, Moskow
Region, Russia
• Los Alamos National Laboratory, USA
• Ben Gurion University of Be’er Sheva, Israel
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Main Collaborations with
Hospital Institutions
• Istituto Europeo di Oncologia, IEO Servizio Radioterapia e
Medicina Nucleare, Milano
• Ospedale San Paolo, Servizio Medicina Nucleare, Milano
• Ospedali Riuniti di Bergamo, Servizi Medicina Nucleare e
Fisica Sanitaria, Bergamo
• Ospedale Maggiore-Policlinico, Laboratorio Ciclotrone,
Milano
• Ospedale Niguarda Ca’ Granda, Servizio Fisica Sanitaria,
Milano
• Istituto Tumori, Milano
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Laboratorio LASA-Segrate
[email protected]
[email protected]
Tel: 02 503 19 500
Dipartimento di Fisica – INFN Sezione di Milano
Via Fratelli Cervi, 201 – 20090 Segrate (MI)
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Theoretical SA(CF) :
SA(CF) = Na  / a.m.
Specific Activity, SA :
SA = Activity of a RN / mass isotopic carrier
Isotopic Carrier :
total number of atoms “isotopic”
with main Radio-Nuclide
(both radioactive and stable)
Isotopic Dilution Factor :
IDF = total number of isotopic atoms
divided
number of atoms of RN
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