13 October 2005Highligths_Physics1 [email protected] [email protected] Production of non-conventional high specific activity radionuclides

13 October 2005 Highligths_Physics [email protected]@mi.infn.it

Production of non-conventional Production of non-conventional high specific activityhigh specific activity radionuclidesradionuclides for for biomedical, toxicological and biomedical, toxicological and

environmental purposesenvironmental purposesFlavia Groppi, Mauro Bonardi, Luigi Gini

Dipartimento di Fisica – UNIMI and INFN Sezione di MilanoL.A.S.A. Via F.lli Cervi, 201 20090 Segrate (MI)

Enzo MenapaceDivisione per le Tecnologie Fisiche Avanzate – ENEA, Bologna

Zeev AlfassiDepartment of Nuclear Engineering, Ben Gurion University, Be’er Sheva , Israel

Boris ZhuikovInstitute for Nuclear Research of Russian Academy of Sciences, Moscow, Russia

Kamel Abbas, Uwe Holzwarth, Neil GibsonInstitute for Health and Consumer Protection, JRC, EC, Ispra (Va)

13 October 2005 Highligths_Physics 2

Main Main Research Research FieldsFields• Studies of non-conventional high specific activity non-conventional high specific activity

radionuclides radionuclides by CyclotronCyclotron and Nuclear ReactorNuclear Reactor• Quality Control of radiopharmaceutical compounds Quality Control of radiopharmaceutical compounds

labelled labelled with short- lived and high specific activity radionuclides: by , and spectrometries, atomic absorption spectrometry, liquid scintillation counting, radioichromatography

• Accelerator Driven Systems for TransmutationAccelerator Driven Systems for Transmutation of Nuclear Wastes

• Determination of actinoidsDetermination of actinoids (U, Th, Np, Pu, Am, DU) in biological and environmental matrices, , and spectrometries


b e ha vio uro f d iffe ren t ch e m ica l

fo rm s o ftra ce e le m e n ts

m etallo-b iochem istry

L o w L eve l a ndL o n g T e rm

E xp osu re (L L E )to u ltra -tra ce e le m e n ts

environm enta ltoxico logy

ra d io d ia g no s tics(S P E C T , P E T )

sys te m ic ra d ion u c lidetu m o u r th era py

nuclear m edicine

som e N C Aradiotracersapplications

Main uses of No Carrier Added Radiotracers


M A IN S TE P S

R ad ion u c lid icP u rity

irrad ia tion con d it ion sop tim isa tion

th ick -ta rg e tyie ld s

th in -ta rg e texc ita tion fu n c tion s

N u c lear R eac tionS tu d ies

u ltra -h ig hp u rity eq u ip m en ts

U ltra -h ig hp u rity ta rg e ts

U ltra -h ig hp u rity ch em ica ls

N .C .A .rad ioch em ica l

p rocess in g

C h em ica lP u rity

S p ec ificA c tivity

R ad ioch em ica lP u rity

R ad ion u c lid icP u rity

Q u a lityC on tro l

Production of a N.C.A. radionuclide

N.C.A.Labelled

compound


Origins of Isotopic Carrier(both stable and radioactive)

in p rac tice"n o t a vo id ab le "

target m ateria la nd target holder

im p u rit ies

ve ry com m onin cyc lo tronirra d ia tion

siden u c lea r re ac tio ns

u se o f glassw arein s te a d o f

in e rt m a te ria ls(i.e : te flon -P F A )

chem ical im puritiesin ta rg e t ra d ioch e m ica l

p ro cess ing

preparationpit fa llsin N C A

radiotracer


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 W-186 target. Radiochemical separation and QC.


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 gammasPET

-camera+ , 4.2 MeV

186gRe 89.25 h 186W (p,n) 186W (d,2n)

137 keVother gammas

SPET

-camera- , 1.1 MeV

211At 211Po

7.22 h

516 ms209Bi (,2n) X 79 keV -camera

, 5.868 MeV , 7.448 MeV

210At 210Po

8.3 h

138.4 d209Bi (,3n) many gammas -camera

internal spike

, 5.304 MeV225Ac 213Bi 213Po

10.0 d

45.6 m

4.2 s

226Ra (p,2n) many gammasSPET

-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


211At production methods

JRC-Euratom Ispra cyclotron

K = 38 Tmax/A = K (Z/A)2

d up to 19 MeVp , up to 38 MeV

direct methods

Bombarding Bi metallic targets with light ions

209Bi(, n)211At

209Bi(, 2n)211At

indirect methods

From the decay of its precursor 211Rn

209Bi(6Li, 4n) 211Rn 211At232Th(p, spall) 211Rn 211At232Th(, spall) 211Rn 211At

I up to 60 A

Beam line Irradiation chamber


Decay scheme of 211At

516 ms

58,2 % 41,8 %

E=5.9 MeV

100 %E=7.5 MeV

stabile207Pb

211gPo

211At 7.214 h

207Bi

31,55 a

100 %

211mPo25,2 s

T1/2ES(MeV)Reaction

8,1 h

7,214 h

28,61209Bi(,3n)210At

20,72209Bi(,2n)211At

138,376 d

138,376 d

138,376 d

21,49209Bi(,d n)210Po

15,11209Bi(,t)210Po

23,76209Bi(,p 2n)210Po

Decay scheme of 210At

100 %(on 206Pb)

138,376 d

210Po

0,175 % (on 206Bi)

99,825 %

210At

8,1 h

E=5,3 MeV

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 m 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.


Dissoluzione del Bi in HNO3 concentrato

Aggiunta alla soluzionedi HCl 8 M

1. Dissoluzione del target irraggiato

Estrazione in solvente organico etere diisopropilico (o tetracloruro di carbonio)

Fase acquosa polonio-210 e Bi

Fase organicaastato-210,211

Lavaggio con HCl 8 M

Ri-estrazione conetere diisopropilico

2.Estrazione liquido/liquido

Resa:98 %

Riduzione in forma anionica dell’astato con agente riducente (cloruro di idrossilammonio)

3. Ri-estrazione in fase acquosa

In alternativa riduzione in forma anionica dell’astato in soluzione basica (NaOH)

Resa:50 %

Resa:90 %

•Radiochemical separations•Nuclear measurements (, , spectrometry)


500 1000 1500 2000101

102

103

104

105

106

107

207Bi1770.23

207Bi1063.67

210At1181.4 1436.71483.6 1599.7

210At245.31

211At669.60 742.64

211At/211gPo897.80

211At687.00

211At/211gPo569.702

211At/211gPo328.12

cou

nts

gamma energy (keV)

HPGe spectrum – 28.8 MeV irradiation

50 60 70 80 90 100 110105

106

107

zoom region211At/211gPo

92.4 keV

89.6 keV

79.3 keV

76.9 keV

coun

ts

gamma energy (keV)


5000 6000 7000 80000

200

400

600

800

1000

1200

after L/L exstraction

7450

.6 k

eV

5867

.7 k

eV

5304

.4 k

eV

210 P

o (

t 1/2=

138

.376

d)

cou

nts

x c

han

nel

s-1

211g

Po

(t 1/

2= 5

16 m

sec)

211 A

t (t

1/2=

7.2

14 h

)

alpha energy (keV)

5000 6000 7000 80000

20

40

60

80

100

120

5304

.4 k

eV

kco

un

ts x

ch

ann

els-1

polonium fractionin aqueous phase

210 P

o (

t 1/2=

138

.376

d)

alpha energy (keV)

5000 6000 7000 80000

30

60

90

120

150

180

210

240

5867

.7 k

eV

7450

.6 k

eV

kco

un

ts x

ch

ann

els-1

astatine fractionin organic phase

211g

Po

(t 1/

2= 5

16 m

sec)

211 A

t (t

1/2=

7.2

14 h

)

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).

alpha spectrum of the astatine fraction (extracted by the organic solvent): At product is completely extracted from the aqueous solution.

alpha spectrum of the separated 210Po fraction (remained in the aqueous phase): none of the 210Po is taken into the organic solvent extraction.


211At210At

209Bi(, 3n)210At209Bi(, 2n)211At


Production of Production of 186186Re via (p,n) reaction on Re via (p,n) reaction on 186186W targetW target

10 20 30

0

20

40

60

80

100

120

140

cro

ss s

ecti

on

(cm

2 x 1

0-27 )

proton incident energy (MeV)

Empire II Szelecsenyi et al. (1997) Shigeta et al.(1996) Zhang et al 1999


Nuclear Physics Laboratory:

4 HPGe connected to 4 MCAs


Nuclear Physics Laboratory:

NaI(Tl), spectrometer, Geiger-Müller Liquid Scintillation Counting


Cold Chemistry Laboratory for trace analysis

UV-VIS spectrophotometry, polarography-SV, ET-AAS radio-TLC, radio-PC radio-HPLC, radio-GC


Warm Radiochemistry Laboratory: Class II


Warm Radiochemistry Laboratory: Class II


Hot Radiochemistry Laboratory: Class II


Main Collaboarations withResearch Centres

• Institute for Health and Consumer Protection, JRC-Ispra, 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


Main Collaborations withHospital InstitutionsHospital 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


[email protected] [email protected]: 02 503 19 500

Dipartimento di Fisica – INFN Sezione di MilanoVia Fratelli Cervi, 201 – 20090 Segrate (MI)

Laboratorio LASA-Segrate


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

Theoretical SA(CF) :SA(CF) = Na / a.m.Specific Activity, SA :

SA = Activity of a RN / mass isotopic carrier

Documents

13 October 2005Highligths_Physics1 [email protected] [email protected] Production of non-conventional high specific activity radionuclides