7
Eur J Nucl Med (1988) 14:393-399 European Nuclear Journal of Medicine © Springer-Verlag 1988 Biokinetics and dosimetry for 19 5Au, evaluated in an animal model Lena Andersson, Lars Hallstadius, and Sven-Erik Strand Department of Radiation Physms, University of Lund, Lasarettet, S-221 85 Lund, Sweden Abstract. The use of the generator produced radionuclide 195mAU, half life 30 s, has become feasible for several differ- ent investigations, e.g. cardiac studies. To assess the ab- sorbed dose from the long lived radionuclide 195Au (the daughter of 195mAn, half life 183 days), a biodistribution study of 195Au was performed in animals. Seven rabbits were injected with eluate from a 19SmHg- 195mAu generator and the retention and the biodistribution of the long lived gold isotope was investigated. The activity was localized mainly in the liver and the kidneys. Transforming the data to man resulted in an absorbed dose from 195Au from 1 elution (approximately 925 MBq 195mAu) of 2.2 mGy to the kidney and 1.3 mGy to the liver and an effective dose equivalent of 0.26 mSv. The total effective dose equivalent from all radionuclides in the eluate (195mAu, 19SAu, 195mHg and *95Hg), was estimated to be 0.65 mSv for a single injec- tion (925 MBq 195mAu). Key words: 195Au_ Biokinetics - Dosimetry - Animal study The short lived radionuclide 195mAu (half life 30 s) was made commercially available a few years ago in the form of a radionuclide generator, parent nuclide 195mHg (Fig. 1). Gold-195m is useful for first pass studies and investigations of lung perfusion and cerebral blood flow (Mena et al. 1983a; Eriksson et al. 1983; Nickel et al. 1983). Because of the short half life, a high activity can be administered, yielding good image quality, and consecutive studies can be carried out within a short time. The eluted 195mAuis, however, contaminated with the parent nuclide, 195mHg, and its other radioactive daughters, see Fig. 1. Since the latter have comparatively long half lives, the patient can receive a significant absorbed dose. In order to correctly assess the absorbed dose, it is essen- tial to study the biodistribution and long term retention of the contaminants. Previous studies have dealt mainly with the short lived gold isotope and, to some extent, the mercury isotopes. Byk-Mallinckrodt (1982) and Castron- ovo (1986) have made some calculations of the absorbed dose from 195Au, but there have been no investigations concerning the biodistribution and longterm retention of 195Au" This work presents an animal study of the retention of 19SAu. Based on the biokinetics, absorbed dose and ef- Offprint requests to: L. Andersson fective dose equivalent have been estimated for standard man using the standard MIRD formalism (Loevinger and Berman 1976). Materials and methods 195mHg-- 195mAu generator. The parent nuclide, 195mHg, is produced by proton irradiation of a 197Au target at a cyclo- tron facility. A simplified decay scheme for 19SmHg and its daughter nuclides is shown in Fig. 1. Mercury-195m de- cays both to 195mAu (46%) and to a95Hg (54%). The recta- stable gold has a half life of 30.6 s and decays to 195Au which then decays to the stable nuclide 19spt. The mercurcy isotope 195Hg decays to 195Au and in 2.2% of the decays to 195mAu. The important nuclide in this case is a95Au with a half life of 183 days, emitting photons of 99 keV and characteristic X-rays of 65 to 78 keV. The generator studied here (Stercow 195m, Byk-Mal- linckrodt CIL B.V., Petten, Holland) consists of a silica gel column coated with zinc sulphide and loaded with 195mHg and 195Hg as mercuric nitrate. Gold is eluted with 2.5 ml thiosulphate pentahydrate - sodium nitrate solution. Elution yields of 28%-30% for 195mAu have been reported (Mena et al. 1983a; Shapiro etal. 1984) for this type of generator. The manufacturer specifies approximately 23% for the particular one used in this study. Between elutions the generator content of the long lived gold isotope, 195Au, grows continuously. In order to keep ~95Hgm (416 h) 978 % '9'Au (183d ) 1100 7 / 19~Pt (stable) Fig. 1. Decay scheme for 195mHg and its daughter products (Le- derer and Shirley 1978; ICRP 1983)

Biokinetics and dosimetry for 195Au, evaluated in an animal model

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Page 1: Biokinetics and dosimetry for 195Au, evaluated in an animal model

Eur J Nucl Med (1988) 14:393-399 European N u c l e a r Journal of

Medicine © Springer-Verlag 1988

Biokinetics and dosimetry for 19 5Au, evaluated in an animal model

Lena Andersson, Lars Hallstadius, and Sven-Erik Strand Department of Radiation Physms, University of Lund, Lasarettet, S-221 85 Lund, Sweden

Abstract. The use of the generator produced radionuclide 195mAU, half life 30 s, has become feasible for several differ- ent investigations, e.g. cardiac studies. To assess the ab- sorbed dose from the long lived radionuclide 195Au (the daughter of 195mAn, half life 183 days), a biodistribution study of 195Au was performed in animals. Seven rabbits were injected with eluate from a 19SmHg- 195mAu generator and the retention and the biodistribution of the long lived gold isotope was investigated. The activity was localized mainly in the liver and the kidneys. Transforming the data to man resulted in an absorbed dose from 195Au from 1 elution (approximately 925 MBq 195mAu) of 2.2 mGy to the kidney and 1.3 mGy to the liver and an effective dose equivalent of 0.26 mSv. The total effective dose equivalent from all radionuclides in the eluate (195mAu, 19SAu, 195mHg and *95Hg), was estimated to be 0.65 mSv for a single injec- tion (925 MBq 195mAu).

Key words: 195Au_ Biokinetics - Dosimetry - Animal study

The short lived radionuclide 195mAu (half life 30 s) was made commercially available a few years ago in the form of a radionuclide generator, parent nuclide 195mHg (Fig. 1). Gold-195m is useful for first pass studies and investigations of lung perfusion and cerebral blood flow (Mena et al. 1983a; Eriksson et al. 1983; Nickel et al. 1983). Because of the short half life, a high activity can be administered, yielding good image quality, and consecutive studies can be carried out within a short time.

The eluted 195mAu is, however, contaminated with the parent nuclide, 195mHg, and its other radioactive daughters, see Fig. 1. Since the latter have comparatively long half lives, the patient can receive a significant absorbed dose.

In order to correctly assess the absorbed dose, it is essen- tial to study the biodistribution and long term retention of the contaminants. Previous studies have dealt mainly with the short lived gold isotope and, to some extent, the mercury isotopes. Byk-Mallinckrodt (1982) and Castron- ovo (1986) have made some calculations of the absorbed dose from 195Au, but there have been no investigations concerning the biodistribution and longterm retention of 195Au"

This work presents an animal study of the retention of 19SAu. Based on the biokinetics, absorbed dose and ef-

Offprint requests to: L. Andersson

fective dose equivalent have been estimated for standard man using the standard MIRD formalism (Loevinger and Berman 1976).

Materials and methods

195mHg-- 195mAu generator. The parent nuclide, 195mHg, is produced by proton irradiation of a 197Au target at a cyclo- tron facility. A simplified decay scheme for 19SmHg and its daughter nuclides is shown in Fig. 1. Mercury-195m de- cays both to 195mAu (46%) and to a95Hg (54%). The recta- stable gold has a half life of 30.6 s and decays to 195Au which then decays to the stable nuclide 19spt. The mercurcy isotope 195Hg decays to 195Au and in 2.2% of the decays to 195mAu. The important nuclide in this case is a95Au with a half life of 183 days, emitting photons of 99 keV and characteristic X-rays of 65 to 78 keV.

The generator studied here (Stercow 195m, Byk-Mal- linckrodt CIL B.V., Petten, Holland) consists of a silica gel column coated with zinc sulphide and loaded with 195mHg and 195Hg as mercuric nitrate. Gold is eluted with 2.5 ml thiosulphate pentahydrate - sodium nitrate solution. Elution yields of 28%-30% for 195mAu have been reported (Mena et al. 1983a; Shapiro etal. 1984) for this type of generator. The manufacturer specifies approximately 23% for the particular one used in this study.

Between elutions the generator content of the long lived gold isotope, 195Au, grows continuously. In order to keep

~95Hgm (41 6 h)

978 %

'9'Au (183 d ) 1100 7 /

19~Pt (stable) Fig. 1. Decay scheme for 195mHg and its daughter products (Le- derer and Shirley 1978; ICRP 1983)

Page 2: Biokinetics and dosimetry for 195Au, evaluated in an animal model

394

the contamination to a minimum and still get the full equi- librium yield of 195mAU, we used an elution interval of 3-5 rain. The generator was used up to three days after manufacture, in accordance with recommendations on use- ful life time (deJong 1983).

Radionuclide purity. The content of gamma emitting nu- clides, other than X95mAu, in the eluate was determined with a Ge(Li) detector. On 5 occasions in connection with the injections of the activity, purity was studied in eluates taken 3 min before and 3 min after the administered eluates.

Animals. Seven rabbits (2.6_+0.7 kg) were anaesthetized with pentobarbital (Mebumal, ACO, Sweden) for 30 min and 400~900 MBq t95mAu from the generator was injected i.v. into an ear vein.

Whole body measurements. The whole body content of t95Au, 195"Hg and 195Hg, was measured in vivo at regular intervals with a standard whole body counter based on a NaI(T1) detector. Separation of the different radionuclides by energy was not possible with this system due to the energy resolution of 35%-40%. The energy window was centered over the characteristic X-ray peaks from both the gold and the mercury isotopes (65 78 keV and 67 80 keV respectively). Measurements were performed once a week during the first month after administration, then once a month until dissection.

Tissue samples. One animal was killed on the following days after administration: 1, 7, 21, 54, 121,187 and 284. Blood samples were taken and liver, kidney, heart, spleen, lung, gonads, thyroid and bone marrow were dissected out. The total organ weight was determined (except for the bone marrow). Using a Ge(Li) detector, the activity content in the tissue samples was measured for each radionuclide, and the organ content at the time of dissection was calculated.

Compartment analysis. The time activity data was analysed on the assumption that the physiological system could be described by a compartment model with first order transfer coefficients. A computer program for such analysis was used (Hallstadius 1986). Starting from an assumed model, the program calculates the set of transfer coefficients that gives the best least squares fit between simulated and ob- served time-activity curves. Different models can be tested in order to find one that conforms to known properties of the real system, and can reproduce observations satisfac- tory. The program also takes into account error propaga- tion, i.e., for each calculated transfer coefficient it specifies the error limits corresponding to the standard deviations assigned to experimental values.

Calculation of absorbed dose. Using the MIRD " S " formal- ism (Snyder et al. 1975), the mean absorbed dose to the organs was calculated according to the equation

5 (rk ~ rh) = -d S (rk ~ rh) (1)

where rk and rh indicate target and source organ, respective- ly. The cumulated activity, A, was estimated from the reten- tion curves obtained from the compartment analysis.

The International Commission on Radiological Protec- tion (ICRP) recommends the use of the effective dose equiv- alent, H~ to estimate risk from irradiation in man (ICRP

1977). The effective dose equivalent is defined as a weighted sum of the mean dose equivalent in a number of specified tissues and in the rest of the body:

HE = ~ w(i) 14(0 (2)

where w(i) is a weighting factor. H(i), the mean dose equiva- lent in tissue i, is given by the mean absorbed dose, I7), weighted by the modifying factors Q and N, where Q is a quality factor depending on the primary radiation. The factor Q is equal to I for photons, N is the product of all other modifying factors, at present assigned the value one.

Results

Radionuclide purity

No contaminants except 19SAu, 195mHg and 195Hg were found in the eluates (detection limit about 0.1-1 Bq per sample). On the first day after manufacture, the t95mHg activity was about 0.9 kBq per MBq 195mAu. By days 2 and 3 the 19SmHg content was 0.3-0.4 kBq/MBq. The a95Hg activity was approximately the same as that of 195mHg. According to the manufacturer, the maximum acceptable level of a95mHg and 195Hg is 1 kBq respectively (Byk-Mal- linckrodt 1982).

Reported mercury contaminations for this type of gen- erator fall in the range 0.2-2 kBq 19SmHg/MBq 195mAu (Mena et al. 1983a, b; de Jong 1983; Byk-Mallinckrodt 1982; Narahara et al. 1984a, b; Mena 1982; Ackers and de Jong 1982; Panek et al. 1982; Wackers et al. 1982).

Whole body measurements

Whole body measurements were evaluated with the com- partment analysis program using the model shown in Fig. 2. Figure 3 shows, for a typical animal, measurements (points)

k(1,3)

19SHgm

k(1,2)

2 k

195Hg

I k(2,3) ,5)

195A 3 < 3

l k{3,4) Known k{1,2) k{2,3)

4 k(3,4) k(1,3) 195pt Unknown k(1,5)= k(2,5) k(3,5)

5

Excreted

Fig. 2. Compartment model adopted for evaluation of the whole body measurements. The 19SAu compartment also includes the short lived 195 mAu

Page 3: Biokinetics and dosimetry for 195Au, evaluated in an animal model

Counts per 5 0 0 s

107 t

10 6

105

10 4

103 [ I I I I I I I I I I I i I I I ~ ~ ~ I , ~ 0 50 100 150 200

Time (days)

Fig. 3. Whole body measurements (points) and the resulting best fit curve (fullfine) obtained from the compartment analysis

and the corresponding best-fit curve (ful l line). Observations represent a weighted sum of 3 compartments, i.e., Nos. 1, 2 and 3 in Fig. 2. The amounts of the respective nuclides in the injected eluates were not measured, since the activity was injected directly f rom the generator, this was, however, calculated by the program. The calculated values were con- sistent with measurements carried out on eluates taken shortly before and after administration. The short lived 195mAu is encompassed in the a9SAu compartment.

Excluding the first week after administration, a biologi- cal half life, hence representing 195Au, of approximately 50 days was found. After day 200 we discern a tendency towards a slower excretion rate, indicating the presence of a small fraction with an even longer retention. F rom the measurements in vivo, we do not know the form or localiza- tion of the latter, nor whether it was initially incorporated as gold or as mercury.

In vitro measurements

The compartment model adopted for evaluation of the biokinetics of 19SAu in the individual organs is shown in Fig. 4. In Figure 5, the fractions o f injected atoms in liver, kidney and blood as a function of time after injection are given.

Most of the administered activity was located in liver, kidney and blood (Table la). Taken together, they con- tained about 60% of the total injected number of atoms at day 7 (hence, less than 50% of the injected material had been excreted during 1 week). The compartment analy- sis was performed on the complete model (Fig. 4), but since these 3 organs were dominant concerning the activity con- tent, a simplified presentation of the result is seen in Fig. 5.

Biological half lives were calculated from the fitted curves. The liver activity, with a biological half life of about 50 days (Table lb), is seen to dominate. In view of the whole body half life of approximately 50 days (above), we conclude that, at least after the 1st week and up to about 200 days, the liver in effect controls the gold retention o f the organism. The tendency towards a slower whole body

395

B l o o d

12 I Liver

I

13 I Kidneys

I

14

I Spleen

I

15

I Lung

I

16 I Heart

I

I 7 Other organs E x c r e t e d

Fig. 4. The compartment model used for evaluation of the tissue samples

Fraction of nlected atoms

10 o

I0-~ ~ Liver

10 -4 I I I I I I I I 1001 I I I I I I I [ I I p r I I I I ]11 200 300

T~e (days)

Fig. 5. The measured retention of 195Au for individual organs (points) and the best fit curve (full hne). Broken line shows the half lives used for the absorbed dose calculations. For the liver this is equal to the full line up to 200 days

excretion after 200 days is poorly reflected in the in vitro data due to large variations between individuals.

Lungs, heart and spleen displayed approximately the same retention pattern as the liver. Their activity content was, however, negligible compared to that of the liver (less than 1% of the injected number of atoms after 1 week).

In order to estimate absorbed dose, the fitted curves for kidneys and blood were split into three (Fig. 5). Between days 7 and 100 a biological half life o f 18 days was used. During this period 98% of the activity was excreted (Tab- le lb). F rom 100 to 200 days we assigned a half life of 50 days and thereafter we made the conservative assump- tion of no excretion. The latter assumption was also made for the liver.

Page 4: Biokinetics and dosimetry for 195Au, evaluated in an animal model

396

Table la. Biodistribution of 195Au

Chemical form Main localization of activity (% of injected activity)

Blood Liver Kidney

Uniformly in the total body

Reference

Au-thiosulfate complex 93 (formed in generator)

Ionic gold (formed inside the body)

Nonionic gold in liver 60 a

Ionic gold Soluble Au-salt

10 a 6 b 25 c

100 13 d 25 d 25 d

75 c 100

Byk-Mallinckrodt 1982

Byk-Mallinckrodt 1982

Brihaye and Guillaume 1983 Hemdal et al. 1983 ICRP 1981 Castronovo 1986 This work

a 20 min after injection b 20 min after injection, increasing. Maximum (t0%-15 %) approximately at day 6 c 22 days after injection

7 days after injection Byk-Mallinckrodt 1982, and ICRP 1981 : time not specified

Table lb. Retention of 195Au

References Biological half life (days)

Organs

Blood Liver Kidney Total body

Byk-Mallinckrodt 1982

Brihaye and Guillaume 1983 a

Castronovo 1986

Hemdal et al. 1983 b

ICRP 1981

This work

10 4

0.19 oo 30

13 (50%) 86 (50%)

O(3

18 (98.2%) 50 (97%) 18 (98.2%) 40 (1.6%) oo (3%) 40 (1.6%) oo (0.2%) ~ (0.2%)

"Values calculated supposing presented values are biological half lifes b From total body measurements

Absorbed dose

The calculated absorbed doses from 195Au after the first week are presented in Table 2a. We obtained the highest dose for the kidneys, 14 mGy per MBq 195Au administered (this unit was introduced to obtain a comprehensive de- scription and represents both 195Au injected as such and 195Au resulting from the decay of parent nuclides, i.e., all injected material is taken as converted to the corresponding amount of ~95Au).

Effective dose equivalent

We obtain an effective dose equivalent due to 195Au of 1.7 mSv/MBq. Tables 2 a-c present an overview of reported absorbed dose due to individual isotopes, and Table 2d shows the total absorbed dose. Values are seen to be in

approximate agreement with the exception of the work by Brihaye and Guillaume (1983).

If we assume that a patient is administered 925 MBq 195mAu (mean activity during the first 2 days after produc- tion) (Byk-Mallinckrodt 1982) and that the contamination level is 1 kBq 19SmHg and 1 kBq 19SHg per MBq 195mAu and 172 Bq ~9SAu/MBq 195mAu (maximum values specified by manufacturer (Byk-Mallinckrodt 1982)), the absorbed doses as calculated by the manufacturer are presented in Table 3. The absorbed dose from 195Au estimated from our work using the activities above is also given in Table 3. In our calculations the absorbed doses refer to the time after the first week.

D i s c u s s i o n

The biodistribution and exchange during the first week after administration fall outside the scope of this work, as does, consequently, the detailed behaviour of the mercury isotopes and the effect of the latter on the gold distribution.

Table la depicts the observed biodistribution of 19SAu. Some studies refer to man and others to animals, and quite different time periods have been considered. Brihaye et al. (1983) have developed their own 195mHg-t95mAu genera- tor and have performed biodistribution studies in rats using 193Au (Zt/2 = 17.6 h) and for longer periods of time (up to 70 days after injection) 195Au was used. The liver con- tained approximately 10% of the injected activity, as they say, probably due to the non ionic gold present at 20% in the eluate. Initially the kidneys contained 6%, increasing to a maximum of 10%-15% 6 days after injection, then decreasing. A slow clearance is shown from both the liver and the kidneys. Brihaye et al. (1983) conclude that the eluted gold can be considered to be mainly a blood pool agent. This study does not take into account the 195Au produced in the generator. Byk-Mallinckrodt (1982) reports that more than 90% of the resulting amount of 195Au (eluted + decay of the mercury isotopes) is eluted from the generator, so this assumption will underestimate the 195Au content about ten times.

Hemdal et al. (1983) carried out measurements on man using a whole body counter and assessed the distribution

Page 5: Biokinetics and dosimetry for 195Au, evaluated in an animal model

Table 2a. Absorbed dose from t95Au

Reference Absorbed dose from 195AL1 (mGy/MBq 195Au)

Liver Kidney Lung Spleen Total body

Effective dose equivalent (mSv)

de Jong 1983 Byk-Mallinckrodt 1982

Hemdal et al. 1983

Castronovo 198&

This work b

1.1

8.2 1.0 1.0 0.9

820

8.2 14 0.38 1.0

0.25

1.0

0.43

1.5

1.7

" Generator design unknown b Absorbed dose from one week after injection

Table 2b. Absorbed dose from 195mAu

References Absorbed dose from 195mAu (gGy/MBq 195mAu)

Liver Kidney Lung Spleen Heart/Heartwall Gonads

Ackers and de Jong 1982 0.032 0,043 Byk-Mallinckrodt 1982 de Jong 1983 Narahara et al. 1984a

Mena 1983b 0,043

Garcia et al. 1981 0.15 Mena et al, 1982

Brihaye and Guillaume 1983 a 0.030 0.054

Dowsett et al. 1985 0,032 0.043

0.15 0.0081 0.21 0.014

0,011 0,032

0.0075

0.020

0.21

0.041

0.014

a Own generator design

Table 2e. Absorbed dose from 195mUg and 195Hg

References Absorbed dose from 19SmUg (including 19SHg)a (mGy/MBq 195mUg)

Liver Kidney Lung Spleen Gonads Total body

Ackers and de Jong (1982 Byk-Mallinckrodt 1982 de Jong 1983 Mena 1983b

0.30 3.4 0.22 0.38 0.22 0.16

a Assuming 1 MBq 195mUg+ 1 MBq 195Hg

Table 2d. The total absorbed dose from a 195mAu eluate

References Absorbed dose from a 195mAu eluate (gGy/MBq 195mAu)

Liver Kidney Lung Spleen Heart/ Gonads Total heartwall body

Byk-Mallinckrodt 1982 de Jong 1983

Narahara et al. 1984a

Ackers and de Jong 1982

Wackers et ai. 1982

Brihaye and Guillaume 1983 a

Dowsett et al. 1985

Lange et al. 1982

Castronovo 1986 b

0.36 3.6 0.36 0.45 0,27 0.27 0.18

3.2

3.4

0.95 4.6 1.2

0.51 0.73 0.95 0.32

0.33 3.6 0.38

5.4

6.3

0.068

0.23 0.16

0,041 ov. 0,095 0.014 test.

a Own generator design b Generator design unknown

Page 6: Biokinetics and dosimetry for 195Au, evaluated in an animal model

398

Table 3. Absorbed dose from one typical injection of a t95mAu-eluate

Reference Radionuclide Activity (MBq)

Absorbed dose (mGy)

Liver Kidney Lung Spleen Heart/ Gonads Total heartwall body

A This work 195Au 0.159

B Byk-Mallinckrodt ~95Au 0.159 C Byk-Mallinckrodt 195mAu 925 D Byk-Mallinckrodt 195mHg 195Hg 0.925 + 0.925

A + C + D Total absorbed dose Effective dose equivalent 0.65 mSv

B + C + D Total absorbed dose Effectave dose equivalent 0.41 mSv

1.32 2.23 0.059 0.16 0.068

0.17 0.040 0.030 0.040 0.14 0.0075 0.19 0.013 0.28 3.1 0.19 0.35 0.19 0.15

1.63 5.37 0.39 0.52 0.19 0.20 0.22

0.31 3.31 0.33 0.36 0.19 0.20 0.19

in vivo by scanning with a collimated detector. It was con- cluded that the major fraction of activity was localized in or near the liver. Scintillation camera measurements a few days after administration also indicated an accumulation of gold in the liver, in accordance with our results.

ICRP (1981) base their value on studies of stable gold, which cannot be expected to give relevant results since a radioactive disintegration may disrupt a chemical bound. The distribution of the daughter nuclide may therefore only initially be equal to the parent nuclide.

Concerning the biodistribution and retention of 195Au, Byk-Mallinckrodt (1982) reports that the 19SAu formed in- side the generator (about 93% of the 195Au activity) will remain in the blood with a biological half life of 10 days. The 19SAu formed inside the body due to decay of the mercury isotopes (about 7%) will be accumulated as ionic gold in the kidney and remain there with a biological half life of 4 days.

Table lb shows the biological half life of 195Au. Byk- Mallinckrodt (1982) presents literature data on biological half lives. The half lives from Brihaye et al. (1983) are esti- mated from their curves representing, we assume, the bio- logical retention. Hemdal et al. (1983) have obtained an initial fast retention from the liver: 50% is excreted with a half life of 13 days. The rest of the activity is more firmly bound and shows a biological half life of 86 days.

Castronovo (1986) has made some dosimetric calcula- tions conserning ~95Au, only considering the fraction of 195Au obtained from the decay of a95mAu and the mercury isotopes and not the 19SAu eluted from the generator. The calculations are made on the assumption that all of this gold is retained in the kidney and that there is no excretion (that is, the effective half life is equal to the physical half life). As seen in Table 2a, the absorbed dose to the kidney per MBq 195Au is estimated to be 820 mGy. This overesti- mation of the absorbed dose will largely be due to the con- servative assumption that there is no biological excretion. Since the calculations have been made for the 195Au ob- tained from the decay of the other radionuclides injected, and not from the fraction of ~9SAu which is eluted from the generator (about 90% of the ~9SAu), the total absorbed dose from the eluate will be comparable with other authors (Table 2 d).

Our values of the absorbed dose are seen to agree fairly well with earlier work except for the kidneys (Table 2a). Also, the value of the effective dose equivalent is in good agreement with the value estimated by Hemdal et al. (1983).

Hemdal has, however, based the calculations on assumed uptake, due to difficulties in localizing the activity from the whole body scanning profile. The study by Byk-Mal- linckrodt (1982) was performed in rats, but no information is given about the duration of the study.

Conclusion

To correctly assess the absorbed dose, it is necessary to perform thorough studies of the biodistribution and reten- tion of the radionuclide and its contaminants.

Table 3 shows that the major contribution to the ab- sorbed dose is due to radionuelide impurities in the eluate. Except for the lungs and the heart, the dose from 195mAu is less than 7% of the total absorbed dose. It is therefore of utmost importance to keep the breakthrough levels as low as possible. Furthermore, a short delay between two consecutive elutions minimizes the build up of 19SAu.

Kidneys are seen to be the critical organs, receiving 3-5 mGy per injection. The total effective dose equivalent is 0.4-0.7 mSv, of which 195Au contributes with 0.026-0.26 mSv. These values can be compared with the effective dose equivalent for 99mTc-pertechnetate used for first pass stu- dies where 400 MBq results in 4.4 mSv (Johansson et al. 1984).

Acknowledgements. This work has been supported by grants from the Swedish Medical Research Council grant No. B85-17X-6530-02 and from the John and Augusta Persson Foundation for Scientific Research, Lund.

References

Ackers JG, de Jong R (1982) Dosimetry consequences of eluates from Hg-195m/Au-195m generators. J Nucl Med 23:P68

Brihaye C, Guillaume M (1983) Properties of a 195mAu generator for cardiovascular imaging. Proceedings of a symposium on Single-photon ultrashort-lived radionuclides. Washington D. C., May %10, pp 232-243

Byk-Mallinckrodt CIL B.V. (1982) Gold in der Nuklearmedizin. Product description. Petten, Holland

Castronovo FP (1986) The 195mAu generator: Radiation burden from 195Au. Health Phys 50:265-269

Dowsett DJ, Ennis JT, Collum CT, de Jong RB (1985) Gold-195m: A steady-state imaging agent for venography that gives blood velocity measurement. J Nucl Med 26:859-867

Eriksson L, Andersson L, Jonson B, Westling H, White T, Wollmer P (1983) Gold-195m for studies on regional pulmonary circula- tion. Proceedings of a symposium on Single-photon ultrashort- hved radionuclides. Washington D. C., May 9-10~ pp 130-136

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Garcia E, Mena I, de Jong R, Fain J (1981) Gold Au-195m, short lived single photon emitter for hemodynamic studies. J Nucl Med 22: P71

Hallstadius L (1986) Compartment modelling in nuclear medicine; a new program for the determination of transfer coefficients. Nucl Med Commun 7:405-414

Hemdal B, Andersson L, J6nsson BA, Earsson I, Mattsson S, Nosslin B (1983) Longtime retention of eluate from a 195mAu- generator (in swedish). Proceedings of Swedish Associations of Nuclear Medicine meeting in Orebro, May 5-6

ICRP (1977) Recommendations of the International Commission on Radiological Protection. Publication 26:21-22

ICRP (1981) Limits for Intakes of Radionuclides by Workers. Pub- lication 30 part 2:57-58

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Received August 15, 1987