The Short-Lived Radionuclide Generator - ACS Symposium Series

13 The Short-Lived Radionuclide Generator Physical Characteristics, Assessment, and Conditions for Optimal Clinical Use

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M.

GUILLAUME

and C .

BRIHAYE

C y c l o t r o n Research Center, Liege University, Belgium

The increasing use o f g e n e r a t o r - p r o d u c e d short-lived radionuclides has c r e a t e d an u r g e n t n e e d for methods t o quantitatively evaluate generator operating characteristics. Daughter nuclide elution yield as a function of e l u a n t flow rate and p a r e n t b r e a k t h r o u g h a r e t h e principal features of a g e n e r a t o r t h a t need t o be d e t e r m i n e d without ambiguity. Standardized generator calibration methods a r e p r o p o s e d and d i s c u s s e d . Clinical r e q u i r e m e n t s must be c o n s i d e r e d in o r d e r to o p t i m i z e the elution f l o w rate in relation t o the total injected v o l u m e , t h e duration o f t h e e x a m i n a t i o n and t h e radiation dose t o t h e patient. V e r y good agreement was o b t a i n e d between theoretical values and d a t a f r o m e x p e r i m e n t a l m o d e l s u s i n g different short-lived daughter nuclides. A radionuclide g e n e r a t o r c a n be d e s c r i b e d as a p a r e n t - d a u g h t e r p a i r from which the daughter n u c l i d e i s s e p a r a t e d from the p a r e n t i n as pure a n u c l e a r f o r m as p o s s i b l e t h r o u g h o u t t h e o p e r a t i n g l i f e of the s y s t e m . A v a r i e t y o f p u b l i c a t i o n s (1-3) h a v e e m p h a s i z e d t h e g e n e r a l p r i n c i p l e s o f t h e m e d i c a l use and q u a l i t a t i v e a s p e c t s of r a d i o n u c l i d e g e n e r a t o r s . The most f r e q u e n t example d i s c u s s e d i s t h e Mo-99/Tc-99m s y s t e m . S t u d i e s o f s h o r t - l i v e d r a d i o n u c l i d e g e n e r a t o r s (4-6) do n o t a d e q u a t e l y t r e a t t h e q u a n t i t a t i v e p r o b l e m s of t h e d a u g h t e r n u c l i d e e l u t i o n or t h o s e s p e c i f i c t o t h e i r o p t i m a l c l i n i c a l use. Two e s s e n t i a l p h y s i c a l c h a r a c t e r i s t i c s of a g e n e r a t o r a r e t h e y i e l d o f t h e d a u g h t e r n u c l i d e and i t s r a d i o c h e m i c a l and r a d i o n u c l i d i c p u r i t y . To r e a l i z e t h e f u l l p o t e n t i a l of a s h o r t - l i v e d r a d i o n u c l i d e generator f o r medical studies r e q u i r e s t h a t t h e s e two c h a r a c t e r i s t i c s a r e o p t i m i z e d and a r e c o m p a t i b l e w i t h p a r a m e t e r s I m p o r t a n t t o c l i n i c a l use s u c h as t o t a l p e r f u s e d volume and d u r a t i o n of t h e s c i n t i g r a p h i c examination. 0097-6156/ 84/ 0241 -0185506.00/ 0 © 1984 American Chemical Society

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

186

RADIONUCLIDE

GENERATORS

Q u a n t i t a t i v e a s s e s s m e n t o f a m e d i c a l g e n e r a t o r must t h e r e f o r e be d e t e r m i n e d by m e t h o d o l o g i e s w h i c h make p o s s i b l e a n i n t e r c o m p a r i s o n o f g e n e r a t o r s used i n d i f f e r e n t l a b o r a t o r i e s and p r o v i d e a b e t t e r u n d e r s t a n d i n g o f t h e p h y s i c o c h e m i c a l a s p e c t s i n v o l v e d . We have t h e r e f o r e p u r s u e d t h e d e v e l o p m e n t and c r i t i c a l a n a l y s i s o f r e l i a b l e methods f o r e v a l u a t i o n of daughter n u c l i d e e l u t i o n y i e l d s which are generally applicable. Such a b s o l u t e and r e p r o d u c i b l e methods are r e q u i r e d f o r the d e t e r m i n a t i o n of i n t r i n s i c generator p a r a m e t e r s w h i c h d e t e r m i n e d a u g h t e r n u c l i d e e l u t i o n y i e l d as w e l l as p a r e n t n u c l i d e d e s o r p t i o n . We have a l s o p r o p o s e d a g e n e r a l methodology f o r a p p l i c a t i o n of c l i n i c a l b o l u s or p e r f u s i o n generators that optimizes simultaneously the a c t i v i t y measurement s t a t i s t i c s i n r e l a t i o n t o t h e d u r a t i o n a n d t h e i n j e c t e d volume. S h o r t - L i v e d Daughter N u c l i d e E l u t i o n Theoretical Considerations. F o r a n u c l e a r p a i r , t h e number o f d a u g h t e r element n u c l e i ( N ) formed by t h e d e c a y o f p a r e n t n u c l e i (Νχ ) v a r i e s as a f u n c t i o n o f t i m e ( t ) as shown i n e q u a t i o n ( 1 ) , where X\ and λ a r e t h e r e s p e c t i v e decay 2

2

*1

N

2

=

Νχ ( e ^ l t λ

2

X

- e* 2t)

(1)

- \\

constants. When λ i s much g r e a t e r t h a n \\ and t i s s m a l l compared w i t h t h e h a l f - l i f e of t h e p a r e n t , r e l a t i o n ( 1 ) r e d u c e s to equation (2). 2

λ

N

2

1 X

=

2

Νχ (1 - e ~ 2 t ) λ

2

I n t e r m s o f r a d i o a c t i v i t y , e q u a t i o n ( 3 ) i s u s e d , where Αχ and A

2

-Αχ

x

(1 - e ~ 2 t )

(3)

A a r e t h e p a r e n t and d a u g h t e r n u c l i d e a c t i v i t i e s , r e s p e c t i v e l y . The maximum v a l u e o f A i s r e a c h e d when t h e t i m e ( t ) i s l o n g compared t o t h e d a u g h t e r n u c l i d e h a l f - l i f e . At t h i s time A = Αχ, i f t h e b r a n c h i n g r a t i o o f t h e p r e c u r s o r i s u n i t y . 2

2

2

E l u t i o n Methods. F o r e v e r y g e n e r a t o r , t h e s e p a r a t i o n of t h e d a u g h t e r n u c l i d e f r o m t h e p a r e n t c a n be p e r f o r m e d by t h e c o n t i n u o u s ( s t e a d y s t a t e ) method o r t h e d i s c o n t i n u o u s ( b o l u s ) method. The c o n t i n u o u s method i n v o l v e s t h e e l u t i o n o f t h e d a u g h t e r n u c l i d e f r o m t h e g e n e r a t o r as i t i s f o r m e d and d i r e c t a d m i n i s t r a t i o n as a gas o r l i q u i d phase. The b o l u s method i n v o l v e s t h e e l u t i o n a t one t i m e of t h e a v a i l a b l e d a u g h t e r


13.

GUILLAUME A N D BRIHAYE

The Short-Lived

Radionuclide

Generator

187

activity. Such discontinuous e l u t i o n s can be performed a f t e r a p p r o p r i a t e i n t e r v e n i n g build-up times. This method must be used when the daughter i s not a s h o r t - l i v e d r a d i o n u c l i d e (Tc-99m). Used i n t h i s way, the generator i s c a l l e d a "cow system." In Figure 1 these two methods are i l l u s t r a t e d by the t i m e - a c t i v i t y p r o f i l e s measured at the output of the generator when e l u t e d at d i f f e r e n t flow r a t e s . The a c t i v i t y peak observed i n the f i r s t seconds of e l u t i o n i s c a l l e d the bolus peak. Within the l i m i t s imposed by the e l u t i o n y i e l d , t h i s a c t i v i t y represents the l e v e l of the daughter i n e q u i l i b r i u m with the parent a v a i l a b l e at the i n i t i a l stage of e l u t i o n . The bolus peak i s followed by a constant e l u t i o n value r e l a t e d to the rate of formation of the daughter a c t i v i t y . The a c t i v i t y e l u t e d during t h i s phase i s determined by the s i z e of the volume being measured. In the extreme case where a large volume i s being counted, the measured e l u t i o n a c t i v i t y i s constant from the beginning and Figure 1 reduces to a s i n g l e h o r i z o n t a l l i n e . The value of the e q u i l i b r i u m l e v e l depends on the formation r a t e of the daughter a c t i v i t y ( A ) . This formation rate (R) i s simply the maximum value of the f u n c t i o n , dA /dt when t = 0, as shown i n equation (4). This r e l a t i o n shows that the maximum 2

2

(dA /dt) 2

= Αχλ

m a x

2

Ξ R (yCi/s)

(4)

l e v e l of r a d i o a c t i v i t y that can be continuously e l u t e d from a generator w i l l increase as the daughter n u c l i d e h a l f - l i f e becomes s h o r t e r . Table I i l l u s t r a t e s that the t h e o r e t i c a l maximum amount of the daughter a c t i v i t y that i s continuously a v a i l a b l e from a 10 mCi generator i s a f u n c t i o n of the h a l f - l i f e of the daughter nuclide. I t i s c l e a r that continuous e l u t i o n i s p a r t i c u l a r l y Table I.

Daughter n u c l i d e

Kr-81m Au-195m Rb-82 Tc-99m

Values of R ( y C i / s ) f o r Several Common Generator Systems*

T

V2 (s)

13 30 78 21600

*Values are c a l c u l a t e d assuming a y i e l d of 100% of a 10 mCi (A ) generator.

R (yCi/s) 533 226 86 0.32 from the e l u t i o n

x


RADIONUCLIDE GENERATORS

BOLUS 30

10

•χ

2

8

BOLUS 15 Ν

Extracting flow rates.

\

\

— \

30 ml/min

— - - 15 ml/min

I

10 m l / m m ν

BOLUS 10

\

Detected volume: 0.25ml Dead volume: 0 10ml

i i i

V

Steady state levels

Extraction time (sec) F i g u r e 1. T i m e - a c t i v i t y perfusion generator.

p r o f i l e o f a 10 mCi Kr-81m


13.

GUILLAUME A N DBRIHAYE

The Short-Lived

Radionuclide

189

Generator

s u i t a b l e f o r s h o r t - l i v e d r a d i o n u c l i d e generators. In the bolus e l u t i o n method when the daughter has no a f f i n i t y f o r the exchanger, as i n the case wih Kr-81m, the t o t a l daughter a c t i v i t y i s e l u t e d i n a minimum of time corresponding to the time r e q u i r e d to empty the free volume of the generator. E l u t i o n Y i e l d Measurement. The e l u t i o n y i e l d i s defined as the r a t i o of the t o t a l e l u t e d a c t i v i t y (TEA) measured under the d e f i n e d experimental c o n d i t i o n s described below to the maximum a v a i l a b l e a c t i v i t y , which i s equivalent (taking i n t o account the branching r a t i o ) to the t o t a l parent a c t i v i t y (Q) present on the column at the time of e l u t i o n . D i f f e r e n t methods were γ

=

(TEA)

(5)

Q s t u d i e d and compared to determine the value of (TEA) i n a manner compatible with the generator used and the p r o p e r t i e s of the daughter n u c l i d e . The i n d i r e c t measurement method c o n s i s t s of the q u a n t i t a t i v e spectrometric measurement of the daughter photopeak, f i r s t on the column at rest and then on the column undergoing e l u t i o n at d i f f e r e n t flow rates of gas or l i q u i d . The e l u t i o n y i e l d i s c a l c u l a t e d i n t h i s case by r e l a t i o n ( 6 ) . This Daughter a c t i v i t y on column during e l u t i o n Maximum daughter

(6)

a c t i v i t y on column at rest

p a r t i c u l a r l y simple method has been adopted by a number of authors. Experience has shown, however, that t h i s method gives experimental values that are c o n s i s t a n t l y too high, e s p e c i a l l y i n the case of l i q u i d phase e l u t i o n . This method assumes that the e l u t i o n y i e l d i s homogeneous at a l l points of the c o l l i m a t e d area being measured and that no f i x a t i o n of the e l u t e d a c t i v i t y occurs on the lower p o r t i o n of the column that i s f r e e of the parent a c t i v i t y . These i d e a l c o n d i t i o n s are v e r y r a r e l y encountered. This method i s t h e r e f o r e to be a p p l i e d with wise reserve, and f o r these reasons, d i r e c t measurement methods of the daughter a c t i v i t y have been developed. The d i r e c t measurement methods to determine the daughter a c t i v i t y proposed here i n v o l v e the measurement of a sample of the e l u t e d daughter a c t i v i t y (SEA) and the determination from these data the value of the (TEA). This i n v o l v e s s o l u t i o n of r e l a t i o n s h i p (7) f o r the experimental c o n d i t i o n s used. Two (TEA) = f (SEA) d i f f e r e n t methods can be a p p l i e d , e i t h e r dynamic or s t a t i c measurement. The experimental c o n d i t i o n s f o r the dynamic


(7)

190


method i n v o l v e t h e s p e c t r o m e t i c measurement of t h e r a d i o a c t i v i t y i n a g i v e n l e n g t h (I2-I1) o f a s m a l l b o r e t u b i n g o r c a t h e t e r f r o m t h e o u t l e t o f t h e g e n e r a t o r , as shown i n F i g u r e 2. I n t h i s c a s e , t h e r e l a t i o n ( 7 ) becomes: (SEA)

2

= (TEA) ( e " * *

1

2

2

- e""* * )

(8)

w i t h t i and t b e i n g t h e e n t r y and e x i t t i m e s o f t h e a c t i v i t y w i t h i n t h e measurement zone, r e s p e c t i v e l y . The v a l u e s of t a r e d e r i v e d from t h e f o l l o w i n g r e l a t i o n s : 2

* ê > \

fcl

-

-tH

2

t2 =

1

*(f) i

^

2

where (f i s t h e i n s i d e d i a m e t e r o f t h e t u b i n g and D t h e f l o w r a t e o f t h e l i q u i d e l u a n t . E q u a t i o n ( 5 ) c a n be r e w r i t t e n a s : ν Q ( e

(SEA) - 2tl _ - 2t X

e

X

(

9

)

2 )

The r e l i a b i l i t y o f t h i s method becomes s u s p e c t f o r s m a l l d i a m e t e r t u b i n g . A t h i g h e l u t i o n f l o w r a t e s and s m a l l t u b i n g d i a m e t e r s , laminar f l o w causes a very sharp v e l o c i t y p r o f i l e w h i c h i n d u c e s a n a p p a r e n t change i n t h e h a l f - l i f e o f t h e m o v i n g radionuclide. I t i s t h e r e f o r e i m p o r t a n t when u s i n g t h i s method t o compare t h e a p p a r e n t h a l f - l i f e o f t h e d a u g h t e r n u c l i d e w i t h the a c t u a l p h y s i c a l h a l f - l i f e . The s t a t i c method o f d a u g h t e r a c t i v i t y measurement c a n be p e r f o r m e d i n t h e c o n t i n u o u s e l u t i o n mode and t h e b o l u s e l u t i o n mode. D u r i n g t h e c o n t i n u o u s s t e a d y - s t a t e e l u t i o n a f t e r p a s s a g e o f t h e b o l u s , a one m i l l i l i t e r sample i s c o l l e c t e d a t t h e column o u t l e t d u r i n g a sampling time of t seconds. A f t e r a w a i t i n g t i m e o f t s e c o n d s , t h e sample i s c o u n t e d by gamma g

s p e c t r o m e t r y f o r 8 t o 10 h a l f - l i v e s . Given i n t h i s case that t£ t and t i • 0, t h e r e l a t i o n s h i p s ( 7 ) and ( 5 ) , become ( 1 0 ) and ( 1 1 ) , r e s p e c t i v e l y . A t y p i c a l c u r v e o f t h e v a r i a t i o n o f β

g

(SEA)

= (TEA) (1 - e "

Q(l-e-

X 2 t

s)

e"

X 2 t

X 2 t s

2

10

) e"* *"

w

< )

U

i

t h e e l u t i o n y i e l d as a f u n c t i o n o f t h e f l o w r a t e i s shown i n F i g u r e 3 f o r a s t a n d a r d Au-195m g e n e r a t o r . The e x p e r i m e n t a l c o n d i t i o n s f o r t h e b o l u s e l u t i o n mode a r e i d e n t i c a l t o t h e c o n d i t i o n s d e s c r i b e d above e x c e p t t h a t t h e sample i s c o l l e c t e d from the b e g i n n i n g of the e l u t i o n . The f i r s t m i l l i l i t e r s contain the e l u t a b l e p o r t i o n of the



The Short-Lived

Radionuclide

Generator

Ge(Li)

Spectrometer

F i g u r e 2. "Tube method" f o r d e t e r m i n i n g r a d i o n u c l i d e generator y i e l d .

Flow rate (ml/min) F i g u r e 3. T y p i c a l c u r v e o f Au-195m e l u t i o n y i e l d e l u t i o n flow rate.

versus


192


a c t i v i t y i n e q u i l i b r i u m w i t h t h e p a r e n t and r e p r e s e n t t h e maximum amount of a c t i v i t y per u n i t volume. R e l a t i o n (7) becomes (SEA)

= (TEA)

e

X

"

2

t

w

(12)

and t h e e l u t i o n y i e l d c a n be e a s i l y c a l c u l a t e d as i n e q u a t i o n ( 5 ) f r o m r e l a t i o n ( 1 3 ) . A d i f f e r e n c e between e l u t i o n y i e l d s γ

bolus

_ÇSEA)_ Λ -Xot Q e *· w

( 1 3 )

d e t e r m i n e d by th e c o n t i n u o u s and b o l u s methods i s m a i n l y due t o a s l o w u p t a k e of t h e d a u g h t e r s p e c i e s by t h e column s u p p o r t . Such a comparison p r o v i d e s a v e r y u s e f u l i n d i c a t i o n of the k i n e t i c s o f t h e exchange of t h e d a u g h t e r n u c l i d e s . Radiochemical P u r i t y -

Breakthrough

A most i m p o r t a n t c h a r a c t e r i s t i c o f a g e n e r a t o r o t h e r t h a n t h e e l u t i o n y i e l d of the d a u g h t e r i s the e x t e n t o f c o n t a m i n a t i o n of t h e e l u a t e by t h e p a r e n t n u c l i d e . This contamination i s d e f i n e d as b r e a k t h r o u g h w h i c h can be c a l c u l a t e d as shown i n e q u a t i o n ( 1 4 ) . B r e a k t h r o u g h i s dependent on t h e d i s t r i b u t i o n

Breakthrough

coefficient

=

P

a

r

e

n

t

a

c

t

l

v

l

t

y e l u t e d / e l u t i o n volume T o t a l p a r e n t a c t i v i t y on t h e c o l u m n

(

( k ^ ) of the p a r e n t on t h e s u p p o r t m a t e r i a l and

U

)

on

t h e c h e m i c a l s t a b i l i t y of the support under h i g h r a d i a t i o n dose. A s a t i s f a c t o r y d i s t r i b u t i o n c o e f f i c i e n t (k,) leads to α p a r e n t a c t i v i t y p r o f i l e s b e f o r e and t h e n a f t e r e l u t i o n w i t h s e v e r a l l i t e r s of s o l u t i o n , as shown i n F i g u r e 4, w h i c h r e f e r s t o t h e Rb-81 p a r e n t a c t i v i t y on a Dowex-50 c o l u m n 15 mm i n length. In such o p t i m a l c o n d i t i o n s the breakthrough i s n e g l i g i b l e «l(T /ml). 6

O p t i m a l C o n d i t i o n s f o r t h e C l i n i c a l Use Generator

of a P e r f u s i o n

F o r t h e a p p l i c a t i o n of a c o n t i n u o u s p e r f u s i o n s y s t e m , i t i s n e c e s s a r y t o know what e l u t i o n r a t e t o use u n d e r s t e a d y s t a t e c o n d i t i o n s i n o r d e r t o m i n i m i z e e i t h e r t h e t o t a l volume of s o l u t i o n t o be i n j e c t e d o r t h e d u r a t i o n of t h e i n j e c t i o n . The p r a c t i c a l o b j e c t i v e of a s c i n t i g r a p h i c - e x a m i n a t i o n i s t o accumulate, i n a g i v e n organ, a s u f f i c i e n t r a d i o a c t i v i t y to p r o d u c e good c o u n t i n g s t a t i s t i c s . An a n a l y t i c a l s t u d y of t h i s p r o b l e m b r i n g s us t o t h e f o r m u l a t i o n o f t h e f o l l o w i n g e q u a t i o n :


The Short-Lived


— —

before any

Radionuclide

8 1 m

Generator

K r extraction

— — — after 500ml of extracting solution at 10 ml/min Pyrex column lenght: 30mm - 0j : 4mm Dowex 50 X 8:100mg(50-150mesh)

S-ir

0

5

10

Distance from column head (mm) Figure

4.

Distribution

p r o f i l e o f Rb a c t i v i t y on a c o l u m n .



194 £ = Q x Y (D) χ ( t - * + j L ~

X 2 t

e

)

(15)

where k

i s the t o t a l cumulative a c t i v i t y (mCi χ min) required by the s c i n t i g r a p h i c examination.

Q

i s the u s e f u l parent load (mCi) on the generator.

Y (D)

λ2 t

i s a f u n c t i o n of the flow rate D and involves the e l u t i o n y i e l d and the decay rate of the daughter i n the t r a n s f e r tubing.

i s the r a d i o a c t i v e decay constant of the daughter. i s the i n j e c t i o n time which can be solved by equation (15).

The values of A depend on the type and c o n d i t i o n s of the s c i n t i g r a p h i c examination and the required q u a l i t y of the image. The Rb-81/Kr-81m generator can be used as an example. Experience has shown that a large f i e l d of view (LFOV) gamma camera equipped with a high r e s o l u t i o n c o l l i m a t o r requires the cumulative a c t i v i t i e s f o r the three t y p i c a l procedures summarized i n Table I I . S o l v i n g equation (15) by succesive Table I I .

Procedure Pneumology Venography Cardiography

Cumulative A c t i v i t y Values of Kr-81m Required f o r T y p i c a l Nuclear Medicine Procedures Q (mCi) 10 30 30

t

(mCi χ min) 7.5 60 150

5

Counts ( 1 0 ) 2.5 1 5

Time (sec) 45 120 300

approximations provides the r e s p e c t i v e p e r f u s i o n durations corresponding to the cumulative a c t i v i t y r e q u i r e d by the medical examination. C a l c u l a t i n g the corresponding volumes of the perfusate s o l u t i o n follows r e a d i l y . For each type of s h o r t - l i v e d generator, a group of monograms can be e s t a b l i s h e d f o r given a c t i v i t i e s loaded on the generator, and A, the cumulative a c t i v i t y required f o r the procedure. A typical example of these monograms i s shown i n Figure 5 f o r a Kr-81m p e r f u s i o n generator (20 mCi of Rb-81) e l u t e d continuously to accumulate a t o t a l cumulative a c t i v i t y of 7, 33 or 100 mCi χ min during the s c i n t i g r a p h i c examination. This example shows that the required p e r f u s i o n duration time decreases very


13.

G U I L L A U M E A N DBRIHAYE

The Short-Lived

Radionuclide

Generator


195

196


r a p i d l y at small e l u t i o n flow r a t e s . Above 7 to 10 ml/min, the decrease i s no longer s i g n i f i c a n t . Minimum i n j e c t i o n volumes are reached between flow rates of 4 to 8 ml/min. At a flow r a t e of 7 ml/min, the Kr-81m e l u t i o n y i e l d i s , f o r example, 70%. The fundamental c o n c l u s i o n of t h i s study i s that the optimal c l i n i c a l e l u t i o n flow rate i n the case of continuous e l u t i o n of a s h o r t - l i v e d r a d i o n u c l i d e from a p e r f u s i o n generator does not n e c e s s a r i l y correspond to the c o n d i t i o n s f o r maximum e l u t i o n y i e l d . This c o n c l u s i o n was confirmed by experimental s t u d i e s with various s h o r t - l i v e d r a d i o n u c l i d e generators such as the Hg-195m/Au-195m and Sr-82/Rb-82 systems. Bolus I n j e c t i o n . The bolus mode c o n s i s t s of the successive p e r f u s i o n s of as many bolus (n) volumes as necessary to reach the cumulative a c t i v i t y & required by the s c i n t i g r a p h i c examination. A mathematical a n a l y s i s of t h i s technique r e s u l t s i n the f o l l o w i n g equation: * -

n

Y

b o l u s Q A 2 ; or η = * X / Y l u s 2

b o

Q

16

( >

T

I f four h a l f - l i v e s ( ly^) occur between two successive bolus e l u t i o n s , the growth of daughter a c t i v i t y w i l l correspond to 94% of the maximum p o s s i b l e per bolus and the t o t a l waiting time w i l l be defined by equation (17). t

t

o

t

- 4 η Ti£ (sec)

(17)

The i n j e c t e d volume corresponding to one bolus i s u s u a l l y quite s m a l l , equivalent at the best to the void volume of the column. The p r i n c i p a l advantage of the repeated bolus method i s that small i n j e c t i o n volumes are r e q u i r e d . On the other hand, perfused a c t i v i t y measurements using small volumes requires high a c t i v i t y generators. Summary D i f f e r e n t p h y s i c a l c o n t r o l procedures are proposed to c a l i b r a t e s h o r t - l i v e d r a d i o n u c l i d e generators and to q u a n t i t a t i v e l y evaluate t h e i r operating parameters. The development of i s o t o p i c generators t a i l o r e d f o r c l i n i c a l use r e q u i r e s that the radiochemist apply such c o n t r o l methods f o r the i n v e s t i g a t i o n and intercomparison of parameters of r e l i a b i l i t y and reproducibility. C l i n i c a l requirements must be taken i n t o account i n order to optimize the e x t r a c t i o n flow r a t e i n r e l a t i o n to the p h y s i c a l c h a r a c t e r i s t i c s of the daughter n u c l i d e and the requirement f o r good counting s t a t i s t i c s i n the imaging procedure.


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The Short-Lived

Radionuclide

Generator

197

Literature Cited 1. 2. 3. 4. 5. 6.

Richards, P. Proc. Symp. Oak Ridge Assoc. Univ. 1965, Chap. 10, 155, U.S.A.E.C., I n f . Serv., 1966. Hnatowich, D. J . I n t . J . Appl. Radiat. losotpes 1977, 28, 169-181. Yano, Y.; Anger, H. O. J . Nucl. Med., 1968, 9, 2-6. Blau, M.; Z i e l i n s k i , R.; Bender, M. Nucleonics 1966, 24, 60-62. Brihaye, C.; Guillaume, M.; L a v i , N.; Cogneau, M. J . Nucl. Med. 1982, 23, 1114-1120. O'Brien, Η., J r . ; Grant, P. M. i n " A p p l i c a t i o n s of Nuclear and Radiochemistry"; R. M. Lambrecht (Ed); Pergamon Press 1982, Chap. 6, 57-60.

RECEIVED

August 19, 1983


The Short-Lived Radionuclide Generator - ACS Symposium Series

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