Radionuclide Generators - American Chemical Society

6 Production of Radionuclides for Generator Systems LEONARD

F.

MAUSNER,

THOMAS

PRACH,

and

POWELL

RICHARDS

Downloaded by UNIV OF CALIFORNIA SAN DIEGO on January 8, 2017 | http://pubs.acs.org Publication Date: January 30, 1984 | doi: 10.1021/bk-1984-0241.ch006

M e d i c a l Department, Brookhaven N a t i o n a l Laboratory, U p t o n , NY 11973

Recently there has been a s i g n i f i c a n t increase i n i n t e r e s t i n generator produced s h o r t - l i v e d r a d i o n u c l i d e s . Developments on three s h o r t - l i v e d p o s i t r o n - e m i t t i n g generator systems which can be produced at the Brookhaven LINAC Isotope Producer (BLIP) are d e s c r i b e d . The Fe-52/Mn-52m p o s i t r o n system is a t t r a c t i v e f o r the study of myocardial p e r f u s i o n because radiomanganese demonstrates good myocardial uptake with extremely r a p i d blood clearance r e s u l t i n g in high myocardium-to-blood r a t i o s . The 21 minute half-life of Mn-52m a l s o allows repeat s t u d i e s to monitor i n t e r v e n t i o n . Our production parameters f o r t h i s generator are presented. The Xe-122/I-122 combination, a convenient source of a s h o r t - l i v e d (3.6m) p o s i t r o n e m i t t i n g i o d i n e , is a l s o d i s c u s s e d . Recent developments i n r a p i d i o d i n a t i o n procedures will broaden the p o t e n t i a l a p p l i c a t i o n s of t h i s generator. F i n a l l y , p r e l i m i n a r y i n v e s t i g a t i o n s of another generator derived r a d i o n u c l i d e that may have promise i s described. Tellurium-118 (6d) is the parent of the 3.5 minute p o s i t r o n e m i t t e r Sb-118 which may be u s e f u l f o r first pass angiography.

The field of n u c l e a r medicine has grown tremendously in the l a s t two decades l a r g e l y as a r e s u l t of the development of the Mo-99/Tc-99m generator system. The ready a v a i l a b i l i t y o f Tc-99m created a mushrooming i n t e r e s t i n n u c l e a r medicine c l i n i c a l and research a c t i v i t y . Technetium-99m i n a v a r i e t y of forms i s annually used i n m i l l i o n s o f n u c l e a r medicine procedures performed worldwide. During recent years there has been a s i g n i f i c a n t increase i n i n t e r e s t i n very s h o r t - l i v e d (10 megohms). The amount o f Iron present i n the f i n a l Fe-52 s o l u t i o n , as determined by atomic a b s o r p t i o n , i s o f the order o f 100-500 ug at end o f bombardment. The s p e c i f i c a c t i v i t y i s higher than 0.15 mCi/ug a t end o f bombardment. A t y p i c a l e l u t i o n curve o f the Fe-52/Mn-52m generator i s shown i n Figure 2. Obviously the y i e l d can be somewhat increased with l a r g e r e l u t i o n volumes. However, since t h i s s o l u t i o n must be evaporated f o r conversion t o acetate some compromise i s necessary. With the column having a 0.6 ml r e s i n bed, approximately 90% o f the generated Mn-52m i s recovered i n 2 ml o f 8N H C l . Figure 3 i s a gamma-ray spectrum o f the e l u t e d Mn-52m obtained using a Ge(Li) detector coupled to a multichannel a n a l y z e r . The r a d i o n u c l i d i c i m p u r i t i e s were determined a f t e r the s h o r t - l i v e d Mn-52m had decayed and no Fe-52 breakthrough was detected. An upper l i m i t o f 1 χ 10~ of Fe-52 breakthrough was d e r i v e d from our minimum d e t e c t a b l e a c t i v i t y of 0.001 u C i . The only a c t i v i t y found was Mn-52 from the decay o f Mn-52m. Manganese-52m decays i n two branches; 97.8% goes t o s t a b l e Cr-52 and 2.2% goes t o 5.67-d Mn-52. Decay-growth c a l c u l a t i o n s i n d i c a t e that 3.2 χ 10~ % o f Mn-52 ( r e l a t i v e t o Mn-52m) i s formed 2

7

4

Knapp and Butler; Radionuclide Generators ACS Symposium Series; American Chemical Society: Washington, DC, 1984.

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RADIONUCLIDE GENERATORS

Table I . Fe-52 Production Parameters

Target M a t e r i a l :

Mn-55(p,4n)Fe-52

Ni-58(p,3p4n)Fe-52

Ep* ( I n c i d e n t )

70 MeV

193.0 MeV

Ep ( E x i t )

50 MeV

191.6 MeV

Production Rate

98 μ Ci/μ Ah

50 μ01/μΑη

T y p i c a l Y i e l d (EOB)

60 mCi

33 mCi

Nuclear Reaction


Nickel (0.45 g/cm?)

Manganese (2.7 g/cmg)

*Proton energy

f Si S

2

3

4

ml OF 8N HCl Figure 2. E l u t i o n p r o f i l e o f t h e Mn-52m g e n e r a t o r . (Re produced w i t h permission from R e f . 5. C o p y r i g h t 1979» Radiological Society of America, Inc.)



MAUSNER ETAL.

Production

•ο Ε

1

of

1

Radionuclides

1

1

1

511 keV

4

'° ^

N ^ N

ι ι ^

!l

s

1 52 m

Γ

Μη

1434 keV

^

3

io k

Ζ) Ο

ο 2

ΙΟ

ιο'

J

100

200

F i g u r e 3.

L

300 400 500 CHANNEL NUMBER

600

700

Mn-52m gamma s p e c t r u m .



84


i n the generator column i n a t y p i c a l growth period o f one hour. Manganese-52 from the decay o f Mn-52m at 118 minutes a f t e r e l u t i o n would amount t o 5.6 χ 10*"**% o f what the Mn-52m had been at time o f e l u t i o n . The presence o f such small amounts would have a n e g l i g i b l e impact on the t o t a l r a d i a t i o n dose t o the p a t i e n t . T h i s work i s a l s o d e t a i l e d by Ku e t a l . (5)· The e l u t i o n y i e l d and i r o n breakthrough were measured as a f u n c t i o n o f time and number o f e l u t i o n s . Six e l u t i o n s were performed over a period o f 26 hours and gave e s s e n t i a l l y constant Mn-52m recovery, averaging 93% o f the a v a i l a b l e r a d i o a c t i v i t y . No i r o n breakthrough was observed from these e l u t i o n s . Utilizing the Fe-59 impurity, breakthrough was checked up t o f i v e days a f t e r end o f bombardment, long past the u s e f u l l i f e o f the generator. There was s t i l l no d e t e c t a b l e i r o n breakthrough. Thus column r e s i n degradation i s minimal and the generator can be s a f e l y used f o r as long as p r a c t i c a l l e v e l s o f r a d i o a c t i v i t y remain. Animal s t u d i e s . D i s t r i b u t i o n data i n animals were obtained u s i n g Mn-54 f o r convenience, administered as the c h l o r i d e and acetate ( 2 ) . Clearance from the blood was extremely r a p i d , w i t h a ti^ o f l e s s than one minute i n dogs (Figure 4 ) . This r e s u l t e d i n a high myocardium-to-blood c o n c e n t r a t i o n r a t i o . The myocardial uptake i n dogs was g r e a t e r than 3%/organ a t three and 15 minutes, with myocardiura-to-blood r a t i o s o f about 40:1 a t 15 minutes. There was good c o r r e l a t i o n ( r » 0.89) between the r e g i o n a l d i s t r i b u t i o n of r a d i o l a b e l e d microspheres and manganese i n the normal and i n f a r c t e d myocardium. P o s i t r o n tomograms were obtained with Mn-52m e l u t e d from the generator described above. These demonstrated r e g i o n a l myocardial p e r f u s i o n i n a normal dog and c l e a r l y v i s u a l i z e d a p e r f u s i o n defect a f t e r l i g a t i o n o f the coronary a r t e r y . Absorbed r a d i a t i o n dose estimates from Mn-52m were c a l c u l a t e d u s i n g b i o d i s t r i b u t i o n from dogs. The dose f o r s e l e c t e d organs was ( i n rad/mCi) whole body 0.032, heart 0.154, blood 0.041, l i v e r 0.291, lungs 0.058, and o v a r i e s 0.068. A subsequent i n v e s t i g a t i o n (6) studied the r e s o l u t i o n and s e n s i t i v i t y o f Mn-52m as a q u a n t i t a t i v e measurement o f the s i z e and l o c a t i o n o f myocardial ischemia. Comparison between microsphere d i s t r i b u t i o n s and Mn-52m images taken a t 1.5 cm l e v e l s revealed that an ischemic area down t o the s i z e of 2.5 cm with 50% o f the normal myocardial p e r f u s i o n can be seen i n the p o s i t r o n images. In a d d i t i o n , a r e l a t i v e change of 10% o r more of the normal p e r f u s i o n i n the ischemic area can a l s o be observed. Large c l i n i c a l s t u d i e s with the Fe-52m/Mn-52m generator have r e c e n t l y been i n i t i a t e d a t the N a t i o n a l Heart and Lung and I n s t i t u t e , National I n s t i t u t e s o f Health, Bethesda, Maryland. 2


MAUSNER ETAL.


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BLOOD CLEARANCE OF RADIOMANGANESE IN DOGS r—ι 1 1 1 1 1 1 1 1 1 1 1 1—•

TIME, min

Figure k. Clearance of (Mn-5MClp from blood i n four dogs (Reproduced with permission from Ref. 2. Copyright 1979» Radiological Society of America, Inc.)


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Xe-122/I-122 A v a r i e t y of r a d i o i s o t o p e s of i o d i n e (1-123, -125, -131) have been shown to be very u s e f u l i n a wide range of medical a p p l i c a t i o n s . However, there remains a gap because of the n o n - a v a i l a b i l i t y of an i o d i n e isotope w i t h a very short h a l f - l i f e f o r repeat s t u d i e s i n sequence with high photon f l u x and low dose. Using a s h o r t - l i v e d i o d i n e l a b e l would thus add these advantages to the long l i s t of e x i s t i n g i o d i n e radiopharmaceuticals. Iodine-122 would appear to f u l f i l l these c r i t e r i a as w e l l as o f f e r i n g the advantage of the q u a n t i t a t i v e e s t i m a t i o n p o s s i b l e with a p o s i t r o n e m i t t i n g n u c l i d e . The decay scheme of the Xe-122/l-122 combination i s shown i n Figure 5. Method. P r e s e n t l y , the parent xenon-122 i s produced i n our l a b o r a t o r y as a by-product i n the production of xenon-123 f o r the preparation of high p u r i t y iodine-123. The target i s a 3.1 g/cm sodium i o d i d e p e l l e t sealed i n a 5 cm diameter Inconel r i n g with 0.025 cm Inconel windows. The target i s i r r a d i a t e d i n the BLIP with 68-48 MeV protons at a beam current of about 50 μΑ· Details of the t a r g e t r y , i r r a d i a t i o n , and processing apparatus have been p r e v i o u s l y reported ( ] ) · M u l t i c u r i e amounts of Xe-123, as w e l l as smaller q u a n t i t i e s of other radioxenons (Table I I ) are produced i n a two-hour bombardment. Although the proton energy i s not optimum f o r the I-127(p,6n)Xe-122 r e a c t i o n , u s e f u l q u a n t i t i e s of Xe-122 can be made with such a short bombardment. The production y i e l d of Xe-122, measured from the a n n i h i l a t i o n gammas of 1-122, i s about 100 mCi at EOB. For a l a r g e r quantity of Xe-122, i t would probably be necessary to lengthen bombardments and increase the proton energy s l i g h t l y . Following the decay p e r i o d which i s required f o r the production of 1-123, the excess xenon a c t i v i t y , i n c l u d i n g xenon-121, -122, -123, -125, and -127, i s t r a n s f e r r e d to a c o l l e c t i o n v e s s e l held at l i q u i d n i t r o g e n temperature. A f t e r waiting s e v e r a l hours to allow Xe-121 ( t ^ « 38.8 minutes) to decay, the remaining xenon i s p u r i f i e d by cryogenic pumping through a 2 cm d i a . χ 5 cm quartz furnace containing titanium sponge (Consolidated A s t r o n a u t i c s , Inc., Long Island C i t y , New York) heated to 800°C. P r i o r to each use, the t i t a n i u m i s thoroughly degassed under vacuum at the same temperature. The xenon isotopes are not a f f e c t e d by the titanium furnace as the noble gases pass through, while traces of other gases are q u a n t i t a t i v e l y removed. T h i s decontamination procedure g r e a t l y improves the e f f i c i e n c y of xenon t r a n s f e r during the 1-122 m i l k i n g process. The xenon i s subsequently condensed and i s o l a t e d i n a storage r e s e r v o i r ready f o r use w i t h the generator. The r e s e r v o i r c o n s i s t s of a bellows v a l v e and a s t a i n l e s s s t e e l tube (0.95 cm O.D., 0.80 cm I.D.). The presence of xenon-127 does not a f f e c t the r a d i o n u c l i d i c q u a l i t y of 1-122 2


6.

Production

MAUSNER ET AL.

Xe-122,

of

87

Radionuclides

- 20.1 h

EC 100%


γ - .350 MeV (8%)

EC

1-122,

β

+

« 3.6 m

77%, EC 23%

γ - .564 MeV (18.4%)

+

β , EC

*Te-122 (stable)

Figure 5.

Xe-122/I-122 decay c h a r a c t e r i s t i c s .

Table I I . Radioxenons Produced by 68 MeV Protons i n Nal

Nuclear

Reaction

Radionuclide

Half-Life

Daughter ( H a l f - l i f e )

(P,n)

Xe-127

36.41 d

1-127 ( s t a b l e )

(p,3n)

Xe-125

17.0

h

1-125 (60.2

d)

(p,5n)

Xe-123

2.08 h

1-123 (13.0

h)

(p,6n)

Xe-122

20.1

h

1-122

(3.6

m)

(p,7n)

Xe-121

38.8

min

1-121

(2.12 h)



88

RADIONUCLIDE

GENERATORS

since i t decays i n t o s t a b l e iodine-127. Iodines from other xenon contaminants such as Xe-123 and Xe-125 are c o n t r o l l e d by the short ingrowth p e r i o d f o r the iodine-122· For example, s t a r t i n g w i t h equal a c t i v i t y l e v e l s of Xe-122, -123 and -125, i f the xenon gas remains i n the decay v e s s e l f o r 5, 10 or 15 minutes, the a c t i v i t y of the daughter i o d i n e s w i l l be i n the r a t i o 100:0.72:0.006, 100:1.08:0.012, and 100:1.35:0.017 f o r 1-122, 123,and 125 r e s p e c t i v e l y . There would be 29% more 1-122 w i t h a 10 minute growth period and 53% more w i t h a 15 minute i n t e r v a l as compared to the 5 minute growth time. Of course, i n a p r a c t i c a l s i t u a t i o n the generator would not be used u n t i l the day a f t e r production so that the l e v e l s of Xe-123, and -125 would be considerably l e s s than assumed i n t h i s example. The generator assembly c o n s i s t s of the above mentioned xenon r e s e r v o i r and a g l a s s m i l k i n g v e s s e l (1.30 cm O.D., 1.05 cm I.D.) (Figure 6 ) . The two are connected by means of an L-shaped s t a i n l e s s s t e e l tube (0.64 cm O.D., 0.45 cm I.D.). The top of the m i l k i n g chamber i s a rubber septum held i n place by an aluminum s e a l . For the purpose of t r a n s f e r r i n g the 1-122 s o l u t i o n out of the chamber, the v e s s e l i s equipped with an inner d e l i v e r y tube (0.64 cm O.D., 0.12 cm I.D.) which i s connected to the o u t l e t side arm (0.64 cm O.D., 0.12 cm I.D.). This tubing points s t r a i g h t down the center with the opening b a r e l y touching the c o n i c a l bottom of the chamber. Attached to the side arm i s mounted a toggle valve which i s used to i s o l a t e the system. The space a v a i l a b l e i n the m i l k i n g chamber i s about 4.5 cm-*. Prior to use, the u n i t i s thoroughly washed with d i s t i l l e d water, methanol, and then vacuum d r i e d . The m i l k i n g procedure i s as f o l l o w s : The m i l k i n g chamber i s evacuated to l e s s than 1 ym and then i s o l a t e d by c l o s i n g the toggle v a l v e . By maintaining t h i s chamber at l i q u i d n i t r o g e n temperature and opening the bellows v a l v e , Xe-122 i s t r a n s f e r r e d i n t o the chamber and condensed onto the g l a s s w a l l . At the end of a f i v e - to ten-minute ingrowth p e r i o d , the l i q u i d n i t r o g e n dewar under the v e s s e l i s replaced with a warm water dewar and at the same time the xenon r e s e r v o i r i s cooled with l i q u i d n i t r o g e n . Xenon immediately t r a n s f e r s back to the r e s e r v o i r while 1-122 remains i n the dewar. The bellows valve i s then closed followed by i n j e c t i n g 2 ml of 1.39% sodium bicarbonate s o l u t i o n through the rubber septum. The toggle valve i s subsequently opened to allow the 1-122 s o l u t i o n to be drawn i n t o a c o l l e c t i o n b o t t l e under vacuum v i a polyethylene tubing. The vacuum a l s o serves to remove any radioxenon remaining i n the u n f i l l e d space i n the b o t t l e . The m i l k i n g operation can be repeated as d e s i r e d by r e p l a c i n g the g l a s s v e s s e l with a p r e t r e a t e d spare u n i t .



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F i g u r e 6. S c h e m a t i c r e p r e s e n t a t i o n o f 1-122 generator. ( R e p r o d u c e d w i t h , p e r m i s s i o n f r o m R e f . 7. C o p y r i g h t 1 9 7 9 , Pergamon P r e s s L t d . )


89


90


The xenon storage r e s e r v o i r and the ingrowth v e s s e l are kept i n two c y l i n d r i c a l l e a d s h i e l d s . The e n t i r e aserably i s constructed on top of a heavy-duty c a r t . The s h i e l d s can be p a r t i a l l y opened f o r the mounting and dismounting of the two u n i t s . The whole m i l k i n g o p e r a t i o n , i n c l u d i n g opening and c l o s i n g the v a l v e s , r a i s i n g and lowering the dewars, and i n j e c t i n g the sodium bicarbonate s o l u t i o n , i s performed with the s h i e l d s closed to provide adequate s h i e l d i n g f o r the operator. This generator i s unique s i n c e once constructed i t remains a t the place of use and i s recharged with Xe-122 as needed by a t t a c h i n g a f r e s h Xe-122 ampoule to the assembly. The only r a d i o n u c l i d i c impurity detected i n the 1-122 i s l e s s than 0.1% radioxenons and other r a d i o i o d i n e s , which n e i t h e r i n t e r f e r e with s c i n t i g r a p h i c imaging nor r e s u l t i n a high r a d i a t i o n exposure to the p a t i e n t . Further improvement of the r a d i o i o d i n e contamination could be a t t a i n e d with an i o d i n e trap between the storage r e s e r v o i r and the growth chamber. The m i l k i n g e f f i c i e n c y i s about 40%. We consider t h i s generator assembly to be a p r e l i m i n a r y v e r s i o n that can be r e f i n e d c o n s i d e r a b l y . Further d e t a i l s may be obtained from Richards and Ku (8). Rapid i o d i n a t i o n s . To f u l l y e x p l o i t the p h y s i c a l advantages o f f e r e d by 1-122, r a p i d i o d i n a t i o n procedures must be developed. These methods must y i e l d high l a b e l i n g e f f i c i e n c y and unchanged b i o l o g i c a l behavior of the l a b e l e d compound. I n i t i a l attempts at r a p i d i o d i n a t i o n s i n t h i s l a b o r a t o r y have produced encouraging r e s u l t s 09). P r e l i m i n a r y e f f o r t s concentrated on lactoperoxidase catalyzed i o d i n a t i o n s and chloramine-T o x i d a t i o n o f i o d i d e . With these procedures i t was demonstrated that 85-95% i o d i n a t i o n y i e l d s with human serum albumin (HSA) i n one to three minutes could be achieved upon a proper s e l e c t i o n of r e a c t i o n c o n d i t i o n s . Using the lactoperoxidase methods under mild c o n d i t i o n s , 1-125 HSA was prepared with 88% y i e l d i n 1 minute, and 96% a f t e r a quick ion-exchange p u r i f i c a t i o n . When i n j e c t e d i n t o dogs, 85% o f t h i s p r e p a r a t i o n remained i n the blood c i r c u l a t i o n a f t e r 60 minutes. S i m i l a r l y , a modified chloramine-T procedure gave a 94% y i e l d , and t h i s product had a blood clearance curve i n dogs very s i m i l a r to that obtained using commercial r a d i o i o d i n a t e d human serum albumin. Despite the short 3.6-minute h a l f - l i f e , p r e l i m i n a r y s t u d i e s i n d i c a t e that the b i o d i s t r i b u t i o n of 1-122 can be followed to determine blood pools of s e l e c t e d organs. The e q u i l i b r a t i o n time f o r the heart blood pool i s l e s s than two minutes; f o r the lung blood p o o l , t h i s t i n e i s even s h o r t e r . Thus, two to three h a l f - l i v e s i s adequate to i n v e s t i g a t e these pools by using 1-122 l a b e l e d albumin. The extension of r a p i d i o d i n a t i o n procedures to l a b e l i n g compounds known to have s p e c i f i c p h y s i o l o g i c a l f u n c t i o n i n other organs would s i g n i f i c a n t l y enhance the usefulness of iodine-122.


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Te-118/Sb-118 At t h i s time our i n t e r e s t i n t h i s p o t e n t i a l generator system i s motivated p r i m a r i l y by the a t t r a c t i v e r a d i o n u c l i d i c p r o p e r t i e s summarized i n Figure 7. Tellurium-118 decays 100% by e l e c t r o n capture with no gamma emissions. The 3.5 minute Sb-118 daughter has very modest gamma emissions; the most s i g n i f i c a n t gamma photon i s only 2.5% abundant (1.230 MeV). A d d i t i o n a l l y , Te-118 represents a bonus since i t can be produced i n an antimony target simultaneously w i t h tin-117m. The BLIP production o f Sn-117m i n a c a r r i e r - f r e e form i s an ongoing p r o j e c t to study the i n - v i v o behavior o f t i n compounds (10). The relevant nuclear r e a c t i o n f o r t e l l u r i u m i s p r i m a r i l y Sb-121(p,4n)Te-118 w i t h some c o n t r i b u t i o n from the (p,6n) r e a c t i o n on Sb-123 (42.7% abundance). The nuclear e x c i t a t i o n functions f o r these r e a c t i o n s have not been measured. A s e r i e s of stacked f o i l i r r a d i a t i o n s i s planned t o determine t h i n target cross s e c t i o n s . This w i l l a l l o w s e l e c t i o n o f optimal bombardment parameters f o r t h i c k target i r r a d i a t i o n a t the BLIP. A c a l c u l a t e d e x c i t a t i o n f u n c t i o n f o r the (p,4n) r e a c t i o n i s shown i n F i g u r e 8. T h i s c a l c u l a t i o n i s based on the i n t e r p o l a t i o n method o f Munzel e t a l . (11) and should allow p r e d i c t i o n o f t h i c k target y i e l d s t o w i t h i n a f a c t o r o f 2 or 3. The no c a r r i e r added chemical separation o f both t e l l u r i u m and t i n from a l a r g e antimony target i s d i f f i c u l t . Dissolving the massive target i t s e l f i s something o f a problem as aqua r e g i a and hot concentrated s u l f u r i c a c i d work o n l y slowly and can lead to i n s o l u b l e p r e c i p i t a t e s without c a r e f u l c o n t r o l o f s o l u t i o n volume and temperature. Instead, concentrated HCl w i t h l i q u i d bromine has been used. This s o l u t i o n i s then d i l u t e d with water to about 2 N HCl. Antimony o x y c h l o r i d e p r e c i p i t a t e s , beginning a t 4jN HCl. Approximately 85% o f the antimony r a d i o a c t i v i t y , most o f the t e l l u r i u m and none o f the t i n are t o be found i n the p r e c i p i t a t e . A f t e r f i l t e r i n g , the f i l t r a t e i s added t o an anion exchange column f o r f u r t h e r p u r i f i c a t i o n o f the tin-117m. The p r e c i p i t a t e i s r e d i s s o l v e d i n concentrated HCl and the s o l u t i o n i s adjusted to about 5N HCl. Selenium c a r r i e r i s added and the s o l u t i o n i s then saturated w i t h SO2 to p r e c i p i t a t e elemental selenium ( c a r r i e s Te r a d i o a c t i v i t y ) . A f t e r f i l t r a t i o n the selenium i s d i s s o l v e d i n concentrated HNO3 and concentrated HBr i s added. T h i s s o l u t i o n i s evaporated by heating t o remove the selenium as SeBr4. The remaining t e l l u r i u m can be d i s s o l v e d i n à small volume o f o x i d i z i n g a c i d . This procedure, although s u c c e s s f u l i s s t i l l being r e f i n e d . The i n v e s t i g a t i o n o f a s u i t a b l e generator column i s now being i n i t i a t e d . A p r e l i m i n a r y non-optimal i r r a d i a t i o n (1 hr) o f a 36 g antimony target was attempted a t an i n c i d e n t energy o f 58 MeV. The measured EOB y i e l d o f Te-118 was 9.5 μCi/gniAh. Thus, Curie q u a n t i t i e s could e a s i l y be produced with a s e v e r a l day bombardment a t 50 μA. P r e l i m i n a r y analyses o f the other t e l l u r i u m r a d i o a c t i v i t i e s produced are summarized i n Table I I I .



Te-118, t, - 6.0 d Downloaded by UNIV OF CALIFORNIA SAN DIEGO on January 8, 2017 | http://pubs.acs.org Publication Date: January 30, 1984 | doi: 10.1021/bk-1984-0241.ch006

h EC 100%

no γ

EC

Sb-118, t ^ « 3.5 m

+

&

75%, EC

γ - 1.230 MeV (2.5%)

+

3 , EC

*Sn-118 (stable)

F i g u r e 7.

Te-118/Sb-118 d e c a y

characteristics.



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MAUSNER ET AL.

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Table I I I . Production Rate of Te Nuclides i n Sb a t 58 MeV (uCi/g-yAh)

Te-118 9.5

Te-119 12.0

Te-121

Te-121m

Te-123

0.54

0.096

0.11




94

Under d i f f e r e n t , optimized r e a c t i o n conditions these q u a n t i t i e s w i l l change. In a generator system Te-123m represents no problem s i n c e i t decays to s t a b l e Te-123 which would remain on the column. A l s o , both Te-121m and Te-121 decay to s t a b l e Sb-121. However, Te-119 leads to Sb-119 which has a h a l f - l i f e of 38 hours. The amount of Sb-119 eluted w i t h the Sb-118 can be minimized by taking advantage of t h e i r l a r g e d i f f e r e n c e i n h a l f - l i f e . That i s , i n o p e r a t i o n a p r e - e l u t i o n should be performed to clean the column of antimony. A f t e r 20 minutes, Sb-118 has regained e q u i l i b r i u m w i t h minimal ingrowth of Sb-119. In t h i s manner the Str-119 can be c o n t r o l l e d to l e s s than 0.7% of the d e s i r e d antimony-118. At t h i s e a r l y stage the primary a p p l i c a t i o n of t h i s generator system appears to be f o r angiography. The 3.5 minute h a l f - l i f e i s more convenient to handle f o r bolus i n j e c t i o n than 30 second gold-195m. Due to f i n i t e c i r c u l a t i o n time, the slower decay should presumably allow b e t t e r imaging of the l e f t v e n t r i c l e . There might a l s o be s u f f i c i e n t time to perform some chemistry on the antimony - perhaps to prepare c o l l o i d s w i t h p o t e n t i a l u t i l i z a t i o n f o r studying l i v e r r e g i o n a l blood flow and clearance. Conclusion Three new p o s i t r o n e m i t t i n g generator systems have been d e s c r i b e d . The p r a c t i c a l a v a i l a b i l i t y of these r a d i o n u c l i d e s could s i g n i f i c a n t l y broaden the p o t e n t i a l a p p l i c a t i o n s of p o s i t r o n emission tomography. The next few years should see human c l i n i c a l t r i a l s undertaken to f u l l y evaluate t h e i r u t i l i t y f o r n u c l e a r medicine. A cknowledgmeηt We would l i k e to acknowledge the support of t h i s work by the U.S. Department of Energy under Contract #DE-AC02-76CH00016. Literature Cited 1.

2. 3.

4.

Chauncey, D.M.; Schelbert, H.R.; Halpern, S.E.; Delano, F.; McKegney, M.L.; Ashburn, W.L.; Hagan, P.L. J. N u c l . Med. 1977, 18, 933-936. A t k i n s , H.L.; Som, P.; F a i r c h i l d , R.G.; H u i , J.; Schachner, E.; Goldman, A.; Ku, T.H. R a d i o l . 1979, 133, 769-774. Atcher, R.W.; Friedman, A.M.; Huizenga, J.R.; Rayudu, G.V.S.; S i l v e r s t e i n , E.A.; Turner, D.A. J . N u c l . Med. 1978, 19, 689. Richards, P.; Lebowitz, E.; Stang, L.G. Radiopharmaceuticals and Labeled Compounds IAEA, Vienna, V o l 1, 1973, 325-341.


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5.

Ku, T.Η.; Richards, P.; Stang, L.G.; Prach, T. R a d i o l . 1979, 132, 475-477. Hui, J . ; A t k i n s , H.L.; Som, P.; Ku, T.H.; F a i r c h i l d , R.G.; Giwa, L.O.; Richards, P. J. Nucl. Med. 1979, 20, 648. Richards, P.; Prach, T.; S r i v a s t a v a , S.C.; Meinken, G.E. J. Radioanal. Chem. 1981, 65, 47-50. Richards, P.; Ku, T.H. I n t . J. Appl. Rad. I s o t . 1979, 30, 250-254. S r i v a s t a v a , S.C., personal communication. S r i v a s t a v a , S.C.; Richards, P.; Meinken, G.E.; Som, P.; Knapp, Jr., F.F.; B u t l e r , T.A. Proc. 3rd World Cong. Nucl. Med. Biol. 1982, p. 1635-1638. Munzel, H.; Lange, J . ; K e l l e r , J.A. "Q-values and e x c i t a t i o n f u n c t i o n s o f nuclear r e a c t i o n s " Landolt-Bornstein New S e r i e s , I 15 Part C.

7. 8. 9. 10. Downloaded by UNIV OF CALIFORNIA SAN DIEGO on January 8, 2017 | http://pubs.acs.org Publication Date: January 30, 1984 | doi: 10.1021/bk-1984-0241.ch006

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August 19, 1983


Radionuclide Generators - American Chemical Society

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