Title
Extraction of astatine isotopes for development of radiopharmaceuticals
using a 211Rn‒211At generator
Author(s)
Maeda, E.; Yokoyama, Akihiko; Taniguchi, T.; Washiyama, K.; Nishinaka,
Ichiro
Citation
Journal of Radioanalytical and Nuclear Chemistry, 303(2): 1465-1468
Issue Date
2014
Type
Journal Article
Text version
author
URL
http://hdl.handle.net/2297/41328
Right
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Ti tl e - Ex tra cti on of a sta tin e i sotop es f or d ev el op men t of
ra di o ph a rma ceu ti ca l s u si n g a
Na me s
-
Ma e d a 1 ,
E.
2 1 1 Rn - 2 1 1 At
A. Yok oy a ma 2 , * ,
g en era tor
T.
Ta ni g u ch i 1 ,
K.
Wa shi y a ma 3 a nd I. N i sh i na k a 4
Aff i l iat io ns –
2 In st.
1
G ra d . S ch ool Na t. S ci . , Tech . K a na za w a U ni v. ,
S ci . Eng . , K an a za w a U n i v.
S ci . , K an a zaw a Un i v.
4 AS RC,
Co rre sp ond in g au th or,
*
3 In st.
Med . Ph a rma . H ea l th
Ja p an Atomi c En erg y Ag en cy
E- ma il : y ok oy a ma @ se.k an a za w a- u .a c. j p
Abst r act – I n o r d er t o ut iliz e a
2 11
At isot ope, a pro mis ing α- e m it t er for
r ad io nu c lide t her ap y, t he che m ica l pr o pert ies o f ast at ine isot o p es ar e
st u d ied.
We ha ve exa m ined wet
che m ist r y met ho ds t hro ugh t he
d ist r ibut io n r at io s o f ast at ine in l iqu id - l iq u id e xt r act io n. T he a st at ine
iso t o p es ha ve bee n fo u nd t o be we l l e xt r act ed int o DI PE and MI B K. We
o bser ved t hat t he d ist r ibu t io n r at io o f a st at ine isot opes incr ease s w it h
co nce nt r at io ns o f HC l gr eat er t ha n 3 M, whi le it decr ease s w it h t he H C l
co nce nt r at io n less t ha n 2 M. T he r esu lt s w il l be use fu l fo r d eve lo p me nt
o f t he
211
Rn- 2 1 1 At g ener at o r.
I nt ro d uct io n
H ig h l y e ner get ic α- par t ic les ar e exp ect ed t o suppr ess t umo r ce ll gr o wt h
e ffic ie nt ly w it h a lo w le ve l o f da mage t o sur ro und ing t issue s bec ause o f
t he ir s hort pat h le ngt hs in t issue s ( <100 μ m) a nd hig h linear e ner g ie s
t r ans fer r ed ( ~100 keV/ μ m) . Amo ng α r ad io nuc l ides,
211
At has gat her ed
at t ent io n as a p ro mis in g α- e mit t er for r ad io nuc l ide t her ap y due t o it s
p h ys ica l ha l f- l i fe o f 7. 2 h. Ast at ine is ot opes mu st be pro duced vi a
nu c lear r eact io ns a nd sep ar at ed fr o m ir r a d iat ed t ar get s w it h hig h pur it y.
But , t he che m ica l pr o p ert ie s o f ast at ine ar e not we ll k no wn fo r t hat
p u r po se. I n or der t o det er mine appr o pr ia t e pro cedur es in pr epar at io n o f
ast at ine us ed in r ad io phar maceut ica ls, we pro duced ast at ine isot o pes b y
t he
r eact io n
of
nat
P b( 7 L i, x n) 2 0 9 - 2 1 1 At
and
eva lu at ed
che m ic a l
sep ar at io ns o f t he isot opes fro m t ar g et mat er ia ls. So lve nt ext r act io n ha s
bee n co n s id er ed o ne o f t he e ffect ive me t ho ds fo r t hat pur po se [ 1]. We
r epo rt d ep end e nce o f t he d ist r ibut io n r at io in so lve nt ext r act io n o f
ast at ine o n t he po lar it y o f or ganic so lve nt s and o n t he co nce nt r at io n o f
HC l. I n add it io n, we pro d uced a r ado n isot ope t o det er mine t he
be ha v io r o f ast at ine iso t o pes gener at ed in t he deca y fr o m r ado n
p r ecur so r s and
ex a min ed
fea s ib il it y o f t hat
che m ica l pr o cedur e.
Ad d it io na ll y, we u sed a b is mut h r ad iot r acer t o r esear c h t he be ha vio r o f
bis mut h at o ms fro m t he t ar get mat er ia l in c he mic a l s epar at io ns o f t he
ast at ine isot o pes.
E xp er ime nt a l
A lead t arget ( 0. 74 mg/ c m 2 ) was ir r ad iat ed w it h 5 0 MeV
7
L i b ea m w it h
a cu r r ent o f 120~200 nA us ing t he JAE A- To ka i t and e m acce ler at o r, t o
p ro du ce ast at ine iso t opes b y t he r eact io n o f
nat
P b( 7 L i, x n) 2 0 9 - 2 1 1 At .
T he ir r ad iat ed t arg et was p ut int o a t est t u be and heat ed up t o 650 ℃
and let st and fo r abo ut 2 0 min in a n e lec t r ic fur nace. T he n car r ier- fr e e
ast at ine wa s sep ar at ed b y d ist illat io n fr o m t he lead t arget . T he n
ast at ine isot opes wer e t r ap ped in 8 M HC l so lu t io n. Ast at ine wa s
ext r act ed fro m t he 8 M HC l so lut io n int o equa l vo lu mes o f se ver a l
o rg an ic so lve nt s wit h var ing po lar it y by s hak ing fo r 5 minut es. T he
γ- act iv it y o f eac h pha se in ext r act io n was measur ed by a HP Ge det ect o r
t o o bt a in t he d ist r ibu t io n r at io o f ast at ine isot o pes.
S u bseq ue nt ly, t he depe nde nce o f t he d i st r ibut io n r at io o f ast at ine o n
t he co nce nt r at io n o f HC l wa s inve st igat ed a ft er ast at ine isot o pes wer e
p ro du ced a nd d ist il led as in t he e xper i me nt descr ibed abo ve. I n t he
p ro ced ur e, ast at ine isot opes wer e t r appe d in 4 M HC l so lut io n, whic h
was t he n ad ju st ed t o se ver a l HC l co nce nt r at io ns bet ween 1 M and 8 M ,
and su bseque nt ly su bject ed t o t he e xt r act io n pr o cess o f a st at ine
iso t o p es w it h a n equa l vo lu me o f DI PE for 5 minut es. T he d ist r ibut io n
r at io s wer e o bt a ined in t he sa me wa y as t he e xper ime nt descr ibe d
abo ve.
I n ad d it io n, t he be ha v io r o f ast at ine gener at ed in t he deca y fr o m t he
r ado n pr ecu r so r was inve st igat ed b y ir r a d iat io n o f bis mut h t arget s ( 3~5
mg/ c m 2 ) w it h 60 MeV
7
L i bea m a nd a cur r ent o f 200 nA us ing t he
JAE A- To k a i t ande m acce ler at o r. We pr oduced r ado n isot o pes b y t he
r eact io n o f
209
B i( 7 L i, 5 n) 2 1 1 Rn. T he ir r ad iat ed t arget was so aked i n
do d ecane so lut io n in a v ia l a nd t he n d is so lved in 6 M HNO 3 so lu t io n
ad d ed t o t he via l. Aft er d is so lving t he bis mut h mat er ia l, ext r act io n o f
t he r ado n pr ecu r so r was p er for med by s hak ing for 1 minut e. Bot h o f t he
p ha ses fro m t he ext r act io n as we ll a s t he ir r ad iat ed t arg et wer e
su b je ct ed t o γ- r a y sp ect ro met r y.
A lead t arg et ( 2 mg/ c m 2 ) was a lso ir r ad i at ed w it h 22 MeV prot o n bea m
at a cu r r ent o f 1000 nA us ing t he AVF c yc lo t ro n o f RCNP in O sak a
u n iv er s it y,
nat
pro duc ing
bis mut h
isot opes
by
t he
r eact io n
of
P b( p , x n) 2 0 5 - 2 0 6 B i. T he ir r ad iat ed t arget was put int o a v ia l w it h a n
o rg an ic so lve nt , t he n it was d isso lved by t he add it io n o f t he 6 M HNO 3 .
Aft er r e mo va l o f t he d is so lv ed t arget , via ls ar e e xt r act ed by s hak ing fo r
1 minu t e. T he d ist r ibut io n r at io s wer e o bt a ined in t he sa me wa y as t he
exp er i me nt descr ibed a bo ve.
Resu lt s
T he ast at ine iso t o pes wer e eff ic ie nt ly e xt r act ed int o d iiso pro p yl et her
( DI P E)
a nd
met h yl
iso bu t yl ket o ne
( MI BK) ,
but
no
s ig nif ica nt
ext r act io n was o bser ved in t o lue ne a nd d ecane as s ho w in F ig. 1. It is
assu med t h at t he e xt r act io n pr o cess o f a st at ine is r e lat ed t o po lar it y o f
t he o rg an ic so lve nt .
Depend e n ce o f t he d ist r ibut io n r at io o n t he co nce nt r at io n o f HC l wa s
o bser ved fo r DI PE as sho w in F ig. 2. I nc r eases in co nce nt r at io n o f HC l
p ro v id ed h ig her d ist r ibut io n r at io s. I n ad d it io n, t he d ist r ibu t io n r at io s
wer e incr ea sed at co nc e nt r at io ns lo wer t ha n 2 M HC l. I n F ig. 3 is sho w n
t he γ- r a y spect r u m o f t he ir r ad iat ed t arget inc lud ing
r eact io n o f
209
2 11
Rn fr o m t he
B i( 7 L i, 5 n) 2 1 1 Rn, a nd t he γ- r a y sp ect r a o f o rganic a nd
aq u eo u s phase s fr o m t he ext r act io n ar e sho wn in F ig. 4 a nd F ig . 5,
r esp ect ive l y, w her e r ado n isot o pes ar e we ll e xt r act ed int o t he o rgani c
p ha se and iso lat ed fro m t he ot her e le me nt s suc h as ast at ine and
po lo n iu m. T he e xper i me nt w it h t he bis m ut h r ad iot r acer suggest ed t hat
ver y s ma l l qua nt it ie s o f bis mut h isot o pes, if a ny, ar e ext r act ed int o
o rg an ic so lve nt fr o m 6 M HNO 3 becau se it s d ist r ibut io n r at io ar e ( 4. 5 ±
0. 2)
×10 - 4
a nd
( 45. 3
±
0. 6)
×10 - 4
fo r
decane
and
do deca ne,
r esp ect ive l y.
D is cu ss io n
T h e d i s t r i b u t i o n r a t i o o f a s t a t i n e w a s p r e vi o u s ly f o u n d t o d e p en d o n t h e
p o l ar i t y of t h e o r g a n ic s o l v en t [ 2 ] , a n d t h a t i s g e n er a l ly c o n s i s t en t w i t h
o ur r e s ul t s . T h e r e s u l t s s u gg e s t t h a t a s t a t i n e c o m p ou n d s h av e a n
e le c tr ic p o l ar i z a t i o n , s o th a t t h ey a r e e a s i ly e x tr a c te d i n t o t h e p ol a r
or g a ni c s o l ve n t s s u c h a s D I P E a n d M I B K . T h e r ef or e , w e f o c u s e d o n t h e
ex t r ac t i o n wi t h D I P E he r e .
Be c a u s e o f t h e r e s u l t s s h o w n i n Fi g . 2 , i t a p p e a r s t h a t a s t a t i n e i s o t o p e s
a r e ex tr a c t e d i n to D I P E d e p e n d in g o n th e c o nc e n tr a t i o n of t h e c h l or i d e
i on i n HC l b e t w e e n 4 M t o 8 M . T h e r e w a s a p r e v i ou s r e p or t a b o u t t h e
s a m e c h l or i d e i on c on c en t r a t i on d e p e n d e nc e . [ 3] T h e ir r e s ul t s a p p e a r t o
b e in c o n s i s t e n t w i t h o ur r e s u l t s a t th e c o nc e n tr a t i o n s o f HC l u n d er 2 M .
T h e r e a s o n of d i s a gr e e m en t i s n o t s t i l l c l e ar. We r e p e a t e d t he s a m e
ex p e r i m e n t t o c on f ir m t h e r e s u l t s . A r o un d t h e c o nc e n tr a t i o n s o f H C l
ex a m i n e d a s t a t i n e i s e x p ec t e d t o f or m a c a t io n ic i on [ 4 ] , s o a s t a t i n e
i on s
are
n e u tr a l i z e d w i t h
the
c o or d i n a t i on
of
c h l or i d e i o n s a n d
ex t r ac t e d in t o or g a ni c ph a s e . O n t he o t h er h a n d , a t c on c e n tr a t i o n s of
HC l b e t w e e n 0 . 1 M t o 2 M , t h e h y dr o ly s i s of a s t a t i n e s p e c i e s m a k e s
t h em n e u tr a l i z e d w i th t h e hy d r ox i d e io n .
So lve nt ext r act io n is co ns ider ed as o ne o f t he mo st e ffect ive met ho ds t o
sep ar at e r ado n isot o pes fro m ma ny by- pro duct s fro m t h e r esu lt s o f
F igs. 3 t o 5. T h e ast at ine isot opes ge ner at ed in t he dec a y fro m r ado n
p r ecur so r can be ba ck- ext r act ed int o ot her so lve nt s.
We ha ve co nf ir med t hat ext r e me ly s ma ll quant it ie s o f b is mut h io ns ar e
ext r act ed int o o rg anic so lve nt in t he c he m ica l pr o cedur e exa m ined.
T his su g gest s t hat t he b is mu t h at o m is in t he fo r m o f a cat io n lik e B i 3 + ,
so t hat it has a st ro ng a ff in it y t o t he wat er p ha se w it h a h ig her po lar it y.
Ou r r esu lt s sho w t hat it is po ss ib le t o r e mo ve t he co nt a minat ing
bis mut h at o ms o f t he t arget mat er ia l dur ing t he iso lat io n o f r ado n
iso t o p es fro m t h e ir r ad iat ed t arg et s.
We be l ie ve t he r esu lt s fr o m t his st ud y w il l be use fu l fo r deve lo p me nt o f
a
2 11
Rn- 2 1 1 At g ener at o r.
Re fer e nce s
[ 1] Neu ma nn H M ( 1957) S OLVE NT DIS T RI BUTI ON ST UDIE S OF
T HE CHE MI S T RY OF AS TAT I NE . I norg Nuc l C he m 4: 349- 353
[ 2] Al lio t C, Chér e l M, Bar bet J, S auvage T, Mo nt avo n G ( 2009)
E xt r act io n o f ast at ine- 211 in d iiso prop yl et her ( DI PE ) . Rad io chi m Act a
9 7 : 1 6 1- 165
[ 3] Na yak D, Lahir i S ( 2003) E xt r act io n separ at io n o f No - car r ier- added
ast at ine fr o m bis mut h t arget . Rad io c him Act a 91: 159- 161
[ 4] Cha mp io n J, S ab at ié- Go go va A, Bass a l F, Ayed T, All io t C, Ga lland
N, Mo nt avo n G ( 2013) I n vest igat io n o f Ast at ine( Ⅲ ) H yd ro lyz ed
S p ec ies: E xp er ime nt s and Re lat ivist ic Ca lcu lat io ns. J P hys C he m A
11 7 : 1 9 83- 1990
F ig u r e capt io n
F ig . 1 D i s t r i b u t i on r a t i o s f o r d if f er e n t p o l ar i t i e s o f o r g a n ic s o l v e n t w i t h
8 M H Cl .
F ig . 2 D i s t r i b u t i o n r a t i o s f o r s e v er a l c o n c e n tr a t i o n s of H C l wi t h D I PE .
F ig . 3 G a mma - r a y s p e c tr u m of
209
2 11
R n p r o d uc e d b y t h e r e a c ti o n of
B i( 7 L i , 5 n ) 2 11 R n .
F ig . 4 G a mma - r a y s p e c tr u m of or g a n ic p h a s e i n d o d ec a n e a f t er
ex t r ac t i o n .
F ig . 5 G a mma - r a y s p e c tr u m of a q u e o u s p h a s e a f t er e x tr a c ti o n .
F ig u r e. 1
MIBK
DIPE
toluene
decane
C 2 H 4 Cl 2
CHCl 3
F ig u r e. 2
Distribution ratio
10
1
0.1
0
2
4
6
Concentration of HCl [M]
8
F ig u r e. 3
F ig u r e. 4
F ig u r e. 5