European Journal of
Nuclear Medicine
Original article
Effective dose from radiopharmaceuticals Lennart Johansson 1, S6ren Mattsson 2, Bertil Nosslin 2 and Sigrid Leide-Svegborn 2 1 Department of Radiation Physics, Ume& University Hospital, S-901 85 Ume&, Sweden Department of Radiation Physics, Maim6 University Hospital, S-214 01 Maim6, Sweden Received 18 April 1992 and in revised from 16 June 1992
Abstract. The effective dose, as defined by the International Commission on Radiological Protection (ICRP 1991), provides a possibility of expressing the radiation risk to patients undergoing different radiodiagnostic procedures by means of a single figure. This has been obtained by introducing organ or tissue weighting factors reflecting the radiation sensitivity of the organs. Such weighting factors were first published by the ICRP in publication 26 (1977), and have now been revised in publication 60 (1991). The effective dose for almost all radiopharmaceuticals in clinical use has been recalculated using the new weighting factors from ICRP 60 (1991) and compared with results from former calculations. A slight decrease in the numerical value for the effective dose has been observed, on average 11%. However, this does not correspond to a decrease in the estimated risk from the irradiation, since this has been re-evaluated and found to be higher than earlier believed (NAS 1990; ICRP 1991).
Key words: Effective dose - Weighting factors - Radio-
to patients from radiopharmaceuticals" (1988), the effective dose equivalents to the patient from different radiopharmaceuticals were given. During the past 14 years, however, our knowledge of the risk of radiation-induced cancer in specific organs has improved. Therefore the ICRP has recently updated publication 26 and presented a revised and extended set of tissue weighting factors in publication 60 (ICRP 1991). In this report the name "effective dose", E, was adopted for the sum of the weighted equivalent doses in the different organs. Even though the ICRP now states that the new weighting factors also may be used for the general public, they are still primarily intended for radiation protection of workers. In 1984 a list of HE values for most radiopharmaceuticals in clinical use was published in this journal (Johansson et al. 1984). The aim of the present paper is to present a similar list of effective doses, E, using the new set of weighting factors, and to compare the results obtained with the new weighting factors with the former "effective dose equivalent".
pharmaceuticals Eur J Nucl Med (1992) 19:933-938
Introduction When in 1977 the ICRP introduced the concept of"effective dose equivalent", HE (ICRP 1977), it was primarily intended to aid in the protection of workers occupationally exposed to radiation. At first the concept was not used for patients undergoing x-ray examinations or investigations involving administration of radiopharmaceuticals. However, the advantage of using only one figure for the comparison of different diagnostic procedures soon led to the calculation of HE for patients, too. In ICRP publication 52 "Protection of the Patient in Nuclear Medicine" (1987) and publication 53, "Radiation dose Correspondence to: L. Johansson
Materials and methods Biological data for the calculation were taken from ICRP 53 (1988), which reports half-times and fractional uptakes for different organs, as well as cumulated activities. In order to calculate the absorbed dose from these data, specific absorbed fractions were taken from Cristy and Eckermann (1987) and physical decay data from the Evaluated Nuclear Structure Data File (ENSDF 1983). The calculations were performed for adults only. The effective dose, E is given by: E=~wr~wrDr, T
R,
R
where WR is the radiation weighting factor, similar to the former Q value, and Dr,e is the absorbed dose in tissue T for radiation R, and wr the organ or tissue weighting factor (Table 1).
Results and discussion In Table 2 the effective dose, E, to adults for all substances and applications included in ICRP 53, is pre-
© Springer-Verlag 1992
934 Table 1. Organ or tissue weighting factors to be used for the calculation of the effective dose according to ICRP 60 (ICRP 1991) Organ or tissue
wr
Gonads
0.20
Lung Red bone marrow Stomach Colon"
0.12 0.12 0.12 0.12
Thyroid Liver Oesophagus Breast Bladder
0.05 0.05 0.05 0.05 0.05
Skin Bone surfaces
0.01 0.01
Remainder
0.05
" "Colon" is here taken to be synonymous with lower large intestine
seated. T h e t a b l e also includes 9 9 m T c - H M P A O , 9 9 m T c - M A G 3 a n d 99mTc-MIBI. P r e l i m i n a r y b i o k i n e t i c a n d d o s i m e t r i c d a t a for these s u b s t a n c e s h a v e been c o m m u n i c a t e d b y the I C R P T a s k G r o u p on U p d a t i n g of I C R P 53. T h e differences b e t w e e n the effective dose as p r e s e n t e d in T a b l e 2 a n d the c o r r e s p o n d i n g effective dose equivalent, HE, c a l c u l a t e d in a c c o r d a n c e with I C R P 26 (1977), are s h o w n in the f o r m of b o x - p l o t s in Fig. 1. T h e HE d a t a used for this c o m p a r i s o n differ o n l y slightly f r o m t h o s e p u b l i s h e d b y J o h a n s s o n et al. (1984). C o m p a r e d with the o l d effective d o s e equivalent, the n u m e r i c a l value of the effective dose for all c o n s i d e r e d s u b s t a n c e s o r a p p l i c a t i o n s h a s d e c r e a s e d b y 11% o n average. F o r the 99mTc-labelled s u b s t a n c e s there has been a n a v e r a g e d e c r e a s e of 2 0 % , while for the i o d i n e - l a b e l l e d s u b s t a n c e s a slight a v e r a g e increase of 3 % is noted. T h e n u m e r i c a l value for the f r e q u e n t l y u s e d 99mTc-labelled p h o s p h a t e s a n d p h o s p h o n a t e s is n o w 2 6 % lower. T h e values for 99mTc-DTPA a n d 9 9 m T c - D M S A have dec r e a s e d b y 13% a n d 4 6 % , respectively, while the figure
Table 2. Effective dose per unit administered activity for radiopharmaceuticals included in ICRP 53 (1988) Radionuclide
Substance
E (mSv/MBq)
3H 3H
Water Inulin
1.5 E - 02 9.4 E - 04
11C 11C 1~C 11C 11C 1~C 11C 14C
1iC_methyl.albumin Carbon monoxide (single inhalation with 20-s breath-hold) Carbon monoxide (continuous inhalation for 1 h) Carbon dioxide (single inhalation with 20-s breath-hold) Carbon dioxide (continuous inhalation for 1 h) COHb-labelled erythrocytes Spiperone Inulin
7.1 E - 03 6.6 E - 03 4.3E-03 1.6E-03 1.0 E - 0 3 4.6 E - 03 5.3 E - 03 8.2E-03
~3N 13N ~3N 13N 13 N
Nitrogen gas (single inhalation with 20s breath-hold) Nitrogen gas (continuous inhalation for 1 h) Nitrogen gas in solution Ammonia I-glutamate
3.8 E - 0 4 4.3 E - 0 4 4.1 E - 0 4 2.0E-03 3.9 E - 03
150 150 15C sO 150 150
Carbon monoxide (single inhalation with 20 s breath-hold) Carbon monoxide (continuous inhalation for 1 h) Carbon dioxide (single inhalation with 20s breath-hold) Carbon dioxide (continuous inhalation for 1 h) Oxygen gas (single inhalation with 20s breath-hold) Oxygen gas (continuous inhalation for 1 h)
1.1 E - 03 7.5 E - 0 4 5.1 E - 0 4 3.8 E - 0 4 4.2E-04 4.7E-04
18F 1s F
Fluoride 2-Fluoro-2-deoxy-d-glucose(FDG)
2.4 E - 02 2.0 E - 02
22Na 2~Na 2~Na
Sodium (intravenous or oral administration) Sodium Sodium (oral administration)
2.6 E + 00 3.2 E - 01 3.6 E - 01
28Mg
Magnesium
7.2 E - 01
32p 3 3p
Phosphate Phosphate
2.4 E + 00 6.6 E - 01
35S
Sulphate
9.0 E - 02
935 Table 2. (continued) Radionuclide
Substance
E (mSv/MBq)
34mc1
Chloride Chloride Chloride
1.4 E - 02 6.7 E - 01 1.4 E - 02
43K ~3K
Potassium (ultrashort-lived) Potassium Potassium (oral administration) Potassium Potassium (oral administration)
1.9 E - 02 2.8 E - 01 3.4 E - 01 2.0 E - 01 2.2E-01
45Ca 45Ca 47Ca ¢7Ca
Calcium Calcium (oral administration) Calcium Calcium (oral administration)
3.1 E + 1.8 E + 1.2 E + 1.8 E +
00 00 00 00
46Sc 46Sc 47Sc 47Sc
Sc-labelled non-absorbable markers Sc-labelled non-absorbable markers Sc-labelled non-absorbable markers Sc-labelled non-absorbable markers
1.6 E + 1.7 E + 7.4 E 7.6 E -
00 00 01 01
51Cr SlCr s 1Cr 51Cr 51Cr 51Cr S~Cr 51Cr 51Cr
Chromium (III) chloride Chromium EDTA Chromium EDTA (oral administration) Cr-labelled platelets (thrombocytes) Cr-labelled erythrocytes Cr-labelled denatured erythrocytes Cr-labelled white blood cells (leucocytes) Cr-labelled non-absorbable markers (fluids) Cr-labelled n0n-absorbable markers (solids)
6.8 E - 02 2.1E-03 4.4 E - 02 1.8 E-- 01 3.2 E - 01 2.1 E - 01 1.5 E--01 4.3 E - 02 4.5 E -- 02
S2Fe 52Fe SSFe s 5Fe 59Fe 59Fe
Iron Iron (oral administration) Iron Iron (oral administration) Iron Iron (oral administration)
3.8E--01 5.7 E - 01 8.5E+01 1.3 E + 00 3.1 E + 0 1 2.7 E + 00
57Co 57Co 58Co s VCo 58Co 5VCo s 8Co 5VCo SSCo
Co-labelled bleomycin Vitamin B12 (intravenous injection with no carrier) Vitamin BI2 (intravenous injection with no carrier) Vitamin B 12 (intravenous injection with carrier) Vitamin ]~12(intravenous injection with carrier) Vitamin B 1z (oral administration with flushing) Vitamin B1 z (oral administration with flushing) Vitamin B~ z (oral administration without flushing) Vitamin B~ z (oral administration without flushing)
4.7 E 4.4 E + 8.2 E + 4.6 E 8~9E 2.1 E + 4.0 E + 3.1 E + 5.9 E +
64Co 67Cu
Copper Copper
3.6 E - 02 1.5 E - 0 1
6ZZn 65Zn
69mZn
Zinc Zinc Zinc
3.5 E - 01 8.4 E + 00 1.4 E - 01
66Ga 67Ga 68Ga 68Ga 72Ga
Gallium Gallium Gallium Gallium Gallium
V2As 74As V6As
Arsenate, arsenite Arsenate, arsenite Arsenate, arsenite
3.6E-01 5.1 E - 0 1 2.8 E - 0 1
75Se 75Se
Selenite Selenomethylcholesterol
2.6 E + 00 1.5 E + 00
36C1 3s C1 3s K 42K
42K
citrate citrate citrate EDTA a citrate
(fluids) (solids) (fluids) (solids)
02 00 00 01 01 00 00 00 00
3.2 E - 01 1.1 E - 01 2.0 E - 02 4.0E--02 3.4 E - 01
936 Table 2. (continued) Radionuclide
Substance
E (mSv/MBq)
75Se 75Se
1-selenomethionine Selenium-labelled bile acid ( S e H C A T )
2.5 E + 00 6.6E 01
76Br v7Br 82 Br vvBr
Bromide Bromide Bromide Bromospiperone
2.8 E - - 0 1 7.7 E -- 02 4.0 E -- 01 8.5 E -- 02
81 ~ K r
Krypton
9.5 E -- 04
81Rb S2Rb SgRb 86Rb 81Rb
Rubidium Rubidium Rubidium Rubidium Rb-labelled d e n a t u r e d erythrocytes
2.8 E - 02 3.4 E - 03 2.8 E + 00 3.0 E + 00 1.4E-01
SSSr 8 VmSr 89Sr
Strontium Strontium Strontium
7.9E 01 6.4 E - 03 3.1 E + 00
99mTc
99mTC 99mTC 99mTC 99mTc 99mTC
Tc-labelled a l b u m i n (HSA) Tc-labelled citrate c o m p l e x Tc-labelled large colloids Tc-labelled small colloids Tc-DMSA Tc-DTPA Tc-labelled p l a s m i n Tc-gluconate, g l u c o h e p t o n a t e Tc-labelled H M P A O a Tc-penicillamine Pertechnetate Pertechnetate (blocking a g e n t given) P e r t e c h n e t a t e (oral a d m i n i s t r a t i o n , no blocking) Tc-labelled I D A derivatives Tc-labelled fibrinogen Tc-labelled erythrocytes Tc-labelled d e n a t u r e d e r y t h r o c y t e s Tc-labelled p h o s p h a t e s a n d p h o s p h o n a t e s Tc-labelled aerosols ( s u b s t a n c e s with fast clearance) Tc-labelled aerosols (substances with slow clearance) Tc-labelled h e p a r i n Tc-labelled M A G 3 " Tc-labelled m a c r o a g g r e g a t e d a l b u m i n Tc-labelled M I B I (rest)" Tc-labelled M I B I (exercise) a Tc-labelled n o n - a b s o r b a b l e m a r k e r s (fluids) Tc-labelled n o n - a b s o r b a b l e m a r k e r s (solids) Tc-labelled a l b u m i n m i c r o s p h e r e s Tc-labelled platelets ( t h r o m b o c y t e s ) Tc-labelled white blood cells (leucocytes)
8.8E 03 6.1 E 03 9.2E--03 9.7 E - 03 8.7 E - 03 5.2 E - 03 9.8 E - 03 5.4 E - 03 9.2E 03 7.3 E -- 03 1.2 E - - 02 4.7 E - - 0 3 1.4 E - 02 1.5 E - - 0 2 9.1E 03 9.8 E - - 0 3 2.3 E - - 0 2 5.8 E - - 0 3 6.1 E - 03 1.4 E - 02 7.2 E - 03 7.2 E - 03 1.1 E - - 0 2 8.5 E - - 0 3 7.5 E - - 0 3 2.0 E -- 02 2.2 E -- 02 1.0E--02 1.6 E - 02 1.4 E - - 0 2
lllIn 113rain t 13rain 11 t In 113rain 1 ~ In 111in t 13rain ~3rain ~~In 11 In 113~in t ~3r, i n
Indium Indium I n d i u m h y d r o x i d e (colloidal) In-DTPA In-DTPA In-aerosols (substances with fast clearance) In-aerosols (substances with slow clearance) In-aerosols (substances with fast clearance) I n - a e r o s o l s (substances with slow clearance) In-labelled n o n - a b s o r b a b l e m a r k e r s (fluids) In-labelled n o n - a b s o r b a b l e m a r k e r s (solids) In-labelled n o n - a b s o r b a b l e m a r k e r s (fluids) In-labelled n o n - a b s o r b a b l e m a r k e r s (solids)
2.1E 01 1.0E--02 1.1 E -- 02 2.1 E -- 02 1.1 E 02 2.5 E -- 02 2.4 E 01 1.6 E -- 02 2.5 E - - 02 3.1 E -- 01 3.2 E - 01 2.0 E - 02 2.9 E -- 02
99mTc 99mTc 99mTc
99mTC 99roTe 99roTe 99mTC 99mTc
99mTC 99mTC 99mTC 99mTc 99roTe 99myc 99mTC 99myc 99~Tc 99mTc
99myc 99mTC 99mTc 99mTC 99rnTc 99mTc
937
Table 2. (continued) Radionuclide
Substance
E (mSv/MBq)
111 In 11 l i n 111In
In-labelled platelets (thrombocytes) In-labelled white blood cells (leucocytes) In-labelled bleomycin
5.2 E - 01 4.7 E - 01 1.0 E - 01
123I 123I 124I 124I 125I ~zsI 131I 311 1231 z3I 125i 1311 123I 2sI 131I 1311 125I 125I t 311 3~I t23I 131I 1231 12 s I 13 t I 1251 t 2sI 1311 12 s I 1311 12s I 1311 1251 131i 1251 311 t 251 1311 1231 1311 1231 1a 11
Iodide (thyroid blocked, uptake 0%) Iodide (thyroid uptake 35%) Iodide (thyroid blocked, uptake 0%) Iodide (thyroid uptake 35 %) Iodide (thyroid blocked, uptake 0%) Iodide (thyroid uptake 35 %) Iodide (thyroid blocked, uptake 0%) Iodide (thyroid uptake 35 %) I o d o a m p h e t a m i n e (IMP) Iodine-labelled flbrinogen Iodine-labelled fibrinogen Iodine-labelled fibrinogen Iodine-labelled albumin (HSA) Iodine-labelled albumin (HSA) Iodine-labelled albumin (HSA) Iodine-labelled m a c r o a g g r e g a t e d albumin (MAA) Iodine-labelled n o n - a b s o r b a b l e markers (fluids) Iodine-labelled n o n - a b s o r b a b l e markers (solids) Iodine-labelled n o n - a b s o r b a b l e markers (fluids) Iodine-labelled n o n - a b s o r b a b l e markers (solids) Iodine-labelled microaggregated albumin (MIAA) Iodine-labelled microaggregated albumin (MIAA) Hippuran Hippuran Hippuran Iodo-antipyrine Iodo-antipyrine Iothalamata Iodomethyl- 19-norcholesterol (NP 59) Iodinated polyvinylpyrrolidone (PVP) Iodinated polyvinylpyrrolidone (PVP) Thyroxine (T4) Thyroxine (T4) Triiodothyronine (T3) Triiodothyronine (T 3) Reverse triiodothyronine (rTa) Reverse triiodothyronine (rT3) Diiodothyronine Diiodothyronine Metaiodobenzylguanidine (MIBG) Metaiodobenzylguanidine (MIBG) Sodium rose bengal Sodium rose bengal
1.1 E - 0 2 2.2E-01 9.5E-02 1.5 E + 01 9.1 E - 0 3 1.4 E + 01 6.1 E - 0 2 2.4 E + 01 2.7 E - 02 2.9 E - 02 1.1 E - 01 5.6 E - 01 2.7E-02 3.1 E - 01 8.2E-01 4.5 E - 01 1.7 E - 0 1 1.7 E - 01 1.2 E + 00 1.2 E + 00 1.8 E - 0 2 2.2 E - 01 1.2 E - 02 7.7 E -- 03 5.3 E -- 02 6.7 E - 02 1.0 E - 02 7.2 E - 03 1.8 E + 00 6.5 E - 01 6.0 E - 01 1.0 E - 01 4.4 E - 01 4.7 E - 02 3.0 E -- 01 3.7 E - 02 2.5 E - 01 3.6 E -- 02 2.5 E - 01 1.4 E - 02 1.4 E - 01 5.9 E - 02 1.1 E + 00
127Xe 133Xe 127Xe 127Xe 33Xe 133Xe
Xenon-gas Xenon-gas Xenon-gas Xenon-gas Xenon-gas Xenon-gas
1.3 E - 0 4 1.8 E - 04 7.1 E - 04 1.1 E - 03 7.3 E - 04 1.1 E - 03
129Cs 130Cs 31Cs t 34mCs
Caesium Caesium Caesium Caesium
4.9 E - 02 3.4 E - 03 5.0E-02 6.7 E - 03
aa 1Ba 133tuBa 135tuBa
Barium Barium Barium
5.0 E - 01 4.7E--01 3.4 E -- 01
311
(single inhalation or i.v. inj., 30-s breath-hold) (single inhalation or i.v. inj., 30-s breath-hold) (rebreathing for 5 rain) (rebreathing for 10 min) (rebreathing for 5 rain) (rebreathing for 10 min)
938 Table 2. (continued) Radionuclide
Substance
E (mSv/MBq)
131Ba 131Ba
Ba-labelled non-absorbable markers (fluids) Ba-labelled non-absorbable markers (solids)
4.9 E - 01 5.1 E - 01
t4°La
La-DTPA
1.5 E - 0 1
169yb
Yb-DTPA
3.6 E - 02
Gold colloid
1.1 E + 00
t97Hg 197Hg 197Hg 2°3Hg
9SAu
Mercury chloride Bromo-mercuri-hydroxypropane (BMHP) Chlormerodrin Chlormerodrin
1.4E-01 1.4 E - 01 8.7 E - 02 1.1 E + 00
2°iT1
Thallium
2.3 E - 01
" Substance not included in ICRP 53
E HE
+ v . _
All ICRP 53
Tc-9'9m
Iodine
Fig. 1. Box-plots of the quotient between the numerical value for the "effective dose", E, calculated with weighting factors according to ICRP publication 60 (1991), and the "effective dose equivalent", He, calculated according to ICRP publication 26 (1977). The line in the shadowed box marks the median value, and the central 50% of the substances are contained within the box. Values falling below the 10th percentile or exceeding the 90th percentile are separately marked for 99mTc-MAG3 is 12% lower. The explanation for these reductions is the different m e t h o d of weighing the " r e m a i n d e r " , where for the old effective dose a weighting factor of 0.06 was given to each of the five m o s t exposed organs. The numerical values for iodide and some orally administered radiopharmaceuticals have increased: those for t23I-, 125I- a n d 131I-iodide have increased by 6 0 % - 7 0 % for a p r e s u m e d t h y r o i d u p t a k e exceeding 10%. There has also been a significant increase for 131I-norcholesterol. These increases m a y be attributed to a higher weighting factor for the t h y r o i d and for the walls of the gastrointestinal tract, respectively. Thus the numerical value of the weighted sum of organ doses has c h a n g e d marginally, even if the change in o r g a n weighting factors has been considerable. This indicates a high degree of robustness of the effective dose values. The estimate of the risk for radiation-induced fatal cancer has, however, increased considerably in the period 1977-1991, f r o m 0.0125 S v - 1 to 0.04 S v - 1 for a p o p u l a -
tion of workers ( I C R P 1991). F o r the total p o p u l a t i o n the risk is estimated to be 0.05 Sv-1. The main reason for this increase is that the "relative m o d e l " for extrapolating the risk into the future ( N A S 1990) is n o w believed to be the m o s t realistic one for m o s t situations. A second reason is the revised dose estimates for the A - b o m b survivors in H i r o s h i m a and Nagasaki. So, in spite of a reduction in the numerical values of the effective dose, due to m o r e realistic o r g a n weighting factors the estimated risk for fatal cancer has m o r e than doubled. It should be a d d e d that, a l t h o u g h the I C R P publication 60 values are used as the basis for current scientific work, the d a t a have yet to be a d o p t e d in national legislation, and so official figures m a y differ from those given in this paper.
References
Cristy M, Eckerman KF (1987) Specific absorbed fractions of energy at various ages from internal photon sources. Report ORNL/ TM-8381/V1 V7. Oak Ridge National Laboratory ENSDF (1983) Evaluated nuclear structure data file, edited and maintained by the National Nuclear Data Center, Brookhaven National Laboratory, on behalf of the International Network for Nuclear Structure Data Evaluation (August 1983). Summary of file contents and published documentation may be found on page iii on any issue of Nuclear Data Sheets ICRP publication 26 (1977) Recomendations of the ICRP. Pergamon, Oxford ICRP publication 52 (1987) Protection of the patient in nuclear medicine. Pergamon, Oxford ICRP publication 53 (1988) Radiation dose to patients from radiopharmaceuticals. Pergamon, Oxford ICRP publication 60 (1991) 1990 recommendations of the international commission on radiological protection. Pergamon, Oxford Johansson L, Mattsson S, Nosslin B (1984) Effective dose equivalent from radiopharmaceuticals. Eur J Nucl Med 9:485~489 NAS (1990) Health effects of exposure to low levels of ionizing radiation. BEIR V report. National Academy of Sciences. National Academy Press, Washington D.C.
Nuclear Medicine
Original article
Effective dose from radiopharmaceuticals Lennart Johansson 1, S6ren Mattsson 2, Bertil Nosslin 2 and Sigrid Leide-Svegborn 2 1 Department of Radiation Physics, Ume& University Hospital, S-901 85 Ume&, Sweden Department of Radiation Physics, Maim6 University Hospital, S-214 01 Maim6, Sweden Received 18 April 1992 and in revised from 16 June 1992
Abstract. The effective dose, as defined by the International Commission on Radiological Protection (ICRP 1991), provides a possibility of expressing the radiation risk to patients undergoing different radiodiagnostic procedures by means of a single figure. This has been obtained by introducing organ or tissue weighting factors reflecting the radiation sensitivity of the organs. Such weighting factors were first published by the ICRP in publication 26 (1977), and have now been revised in publication 60 (1991). The effective dose for almost all radiopharmaceuticals in clinical use has been recalculated using the new weighting factors from ICRP 60 (1991) and compared with results from former calculations. A slight decrease in the numerical value for the effective dose has been observed, on average 11%. However, this does not correspond to a decrease in the estimated risk from the irradiation, since this has been re-evaluated and found to be higher than earlier believed (NAS 1990; ICRP 1991).
Key words: Effective dose - Weighting factors - Radio-
to patients from radiopharmaceuticals" (1988), the effective dose equivalents to the patient from different radiopharmaceuticals were given. During the past 14 years, however, our knowledge of the risk of radiation-induced cancer in specific organs has improved. Therefore the ICRP has recently updated publication 26 and presented a revised and extended set of tissue weighting factors in publication 60 (ICRP 1991). In this report the name "effective dose", E, was adopted for the sum of the weighted equivalent doses in the different organs. Even though the ICRP now states that the new weighting factors also may be used for the general public, they are still primarily intended for radiation protection of workers. In 1984 a list of HE values for most radiopharmaceuticals in clinical use was published in this journal (Johansson et al. 1984). The aim of the present paper is to present a similar list of effective doses, E, using the new set of weighting factors, and to compare the results obtained with the new weighting factors with the former "effective dose equivalent".
pharmaceuticals Eur J Nucl Med (1992) 19:933-938
Introduction When in 1977 the ICRP introduced the concept of"effective dose equivalent", HE (ICRP 1977), it was primarily intended to aid in the protection of workers occupationally exposed to radiation. At first the concept was not used for patients undergoing x-ray examinations or investigations involving administration of radiopharmaceuticals. However, the advantage of using only one figure for the comparison of different diagnostic procedures soon led to the calculation of HE for patients, too. In ICRP publication 52 "Protection of the Patient in Nuclear Medicine" (1987) and publication 53, "Radiation dose Correspondence to: L. Johansson
Materials and methods Biological data for the calculation were taken from ICRP 53 (1988), which reports half-times and fractional uptakes for different organs, as well as cumulated activities. In order to calculate the absorbed dose from these data, specific absorbed fractions were taken from Cristy and Eckermann (1987) and physical decay data from the Evaluated Nuclear Structure Data File (ENSDF 1983). The calculations were performed for adults only. The effective dose, E is given by: E=~wr~wrDr, T
R,
R
where WR is the radiation weighting factor, similar to the former Q value, and Dr,e is the absorbed dose in tissue T for radiation R, and wr the organ or tissue weighting factor (Table 1).
Results and discussion In Table 2 the effective dose, E, to adults for all substances and applications included in ICRP 53, is pre-
© Springer-Verlag 1992
934 Table 1. Organ or tissue weighting factors to be used for the calculation of the effective dose according to ICRP 60 (ICRP 1991) Organ or tissue
wr
Gonads
0.20
Lung Red bone marrow Stomach Colon"
0.12 0.12 0.12 0.12
Thyroid Liver Oesophagus Breast Bladder
0.05 0.05 0.05 0.05 0.05
Skin Bone surfaces
0.01 0.01
Remainder
0.05
" "Colon" is here taken to be synonymous with lower large intestine
seated. T h e t a b l e also includes 9 9 m T c - H M P A O , 9 9 m T c - M A G 3 a n d 99mTc-MIBI. P r e l i m i n a r y b i o k i n e t i c a n d d o s i m e t r i c d a t a for these s u b s t a n c e s h a v e been c o m m u n i c a t e d b y the I C R P T a s k G r o u p on U p d a t i n g of I C R P 53. T h e differences b e t w e e n the effective dose as p r e s e n t e d in T a b l e 2 a n d the c o r r e s p o n d i n g effective dose equivalent, HE, c a l c u l a t e d in a c c o r d a n c e with I C R P 26 (1977), are s h o w n in the f o r m of b o x - p l o t s in Fig. 1. T h e HE d a t a used for this c o m p a r i s o n differ o n l y slightly f r o m t h o s e p u b l i s h e d b y J o h a n s s o n et al. (1984). C o m p a r e d with the o l d effective d o s e equivalent, the n u m e r i c a l value of the effective dose for all c o n s i d e r e d s u b s t a n c e s o r a p p l i c a t i o n s h a s d e c r e a s e d b y 11% o n average. F o r the 99mTc-labelled s u b s t a n c e s there has been a n a v e r a g e d e c r e a s e of 2 0 % , while for the i o d i n e - l a b e l l e d s u b s t a n c e s a slight a v e r a g e increase of 3 % is noted. T h e n u m e r i c a l value for the f r e q u e n t l y u s e d 99mTc-labelled p h o s p h a t e s a n d p h o s p h o n a t e s is n o w 2 6 % lower. T h e values for 99mTc-DTPA a n d 9 9 m T c - D M S A have dec r e a s e d b y 13% a n d 4 6 % , respectively, while the figure
Table 2. Effective dose per unit administered activity for radiopharmaceuticals included in ICRP 53 (1988) Radionuclide
Substance
E (mSv/MBq)
3H 3H
Water Inulin
1.5 E - 02 9.4 E - 04
11C 11C 1~C 11C 11C 1~C 11C 14C
1iC_methyl.albumin Carbon monoxide (single inhalation with 20-s breath-hold) Carbon monoxide (continuous inhalation for 1 h) Carbon dioxide (single inhalation with 20-s breath-hold) Carbon dioxide (continuous inhalation for 1 h) COHb-labelled erythrocytes Spiperone Inulin
7.1 E - 03 6.6 E - 03 4.3E-03 1.6E-03 1.0 E - 0 3 4.6 E - 03 5.3 E - 03 8.2E-03
~3N 13N ~3N 13N 13 N
Nitrogen gas (single inhalation with 20s breath-hold) Nitrogen gas (continuous inhalation for 1 h) Nitrogen gas in solution Ammonia I-glutamate
3.8 E - 0 4 4.3 E - 0 4 4.1 E - 0 4 2.0E-03 3.9 E - 03
150 150 15C sO 150 150
Carbon monoxide (single inhalation with 20 s breath-hold) Carbon monoxide (continuous inhalation for 1 h) Carbon dioxide (single inhalation with 20s breath-hold) Carbon dioxide (continuous inhalation for 1 h) Oxygen gas (single inhalation with 20s breath-hold) Oxygen gas (continuous inhalation for 1 h)
1.1 E - 03 7.5 E - 0 4 5.1 E - 0 4 3.8 E - 0 4 4.2E-04 4.7E-04
18F 1s F
Fluoride 2-Fluoro-2-deoxy-d-glucose(FDG)
2.4 E - 02 2.0 E - 02
22Na 2~Na 2~Na
Sodium (intravenous or oral administration) Sodium Sodium (oral administration)
2.6 E + 00 3.2 E - 01 3.6 E - 01
28Mg
Magnesium
7.2 E - 01
32p 3 3p
Phosphate Phosphate
2.4 E + 00 6.6 E - 01
35S
Sulphate
9.0 E - 02
935 Table 2. (continued) Radionuclide
Substance
E (mSv/MBq)
34mc1
Chloride Chloride Chloride
1.4 E - 02 6.7 E - 01 1.4 E - 02
43K ~3K
Potassium (ultrashort-lived) Potassium Potassium (oral administration) Potassium Potassium (oral administration)
1.9 E - 02 2.8 E - 01 3.4 E - 01 2.0 E - 01 2.2E-01
45Ca 45Ca 47Ca ¢7Ca
Calcium Calcium (oral administration) Calcium Calcium (oral administration)
3.1 E + 1.8 E + 1.2 E + 1.8 E +
00 00 00 00
46Sc 46Sc 47Sc 47Sc
Sc-labelled non-absorbable markers Sc-labelled non-absorbable markers Sc-labelled non-absorbable markers Sc-labelled non-absorbable markers
1.6 E + 1.7 E + 7.4 E 7.6 E -
00 00 01 01
51Cr SlCr s 1Cr 51Cr 51Cr 51Cr S~Cr 51Cr 51Cr
Chromium (III) chloride Chromium EDTA Chromium EDTA (oral administration) Cr-labelled platelets (thrombocytes) Cr-labelled erythrocytes Cr-labelled denatured erythrocytes Cr-labelled white blood cells (leucocytes) Cr-labelled non-absorbable markers (fluids) Cr-labelled n0n-absorbable markers (solids)
6.8 E - 02 2.1E-03 4.4 E - 02 1.8 E-- 01 3.2 E - 01 2.1 E - 01 1.5 E--01 4.3 E - 02 4.5 E -- 02
S2Fe 52Fe SSFe s 5Fe 59Fe 59Fe
Iron Iron (oral administration) Iron Iron (oral administration) Iron Iron (oral administration)
3.8E--01 5.7 E - 01 8.5E+01 1.3 E + 00 3.1 E + 0 1 2.7 E + 00
57Co 57Co 58Co s VCo 58Co 5VCo s 8Co 5VCo SSCo
Co-labelled bleomycin Vitamin B12 (intravenous injection with no carrier) Vitamin BI2 (intravenous injection with no carrier) Vitamin B 12 (intravenous injection with carrier) Vitamin ]~12(intravenous injection with carrier) Vitamin B 1z (oral administration with flushing) Vitamin B1 z (oral administration with flushing) Vitamin B~ z (oral administration without flushing) Vitamin B~ z (oral administration without flushing)
4.7 E 4.4 E + 8.2 E + 4.6 E 8~9E 2.1 E + 4.0 E + 3.1 E + 5.9 E +
64Co 67Cu
Copper Copper
3.6 E - 02 1.5 E - 0 1
6ZZn 65Zn
69mZn
Zinc Zinc Zinc
3.5 E - 01 8.4 E + 00 1.4 E - 01
66Ga 67Ga 68Ga 68Ga 72Ga
Gallium Gallium Gallium Gallium Gallium
V2As 74As V6As
Arsenate, arsenite Arsenate, arsenite Arsenate, arsenite
3.6E-01 5.1 E - 0 1 2.8 E - 0 1
75Se 75Se
Selenite Selenomethylcholesterol
2.6 E + 00 1.5 E + 00
36C1 3s C1 3s K 42K
42K
citrate citrate citrate EDTA a citrate
(fluids) (solids) (fluids) (solids)
02 00 00 01 01 00 00 00 00
3.2 E - 01 1.1 E - 01 2.0 E - 02 4.0E--02 3.4 E - 01
936 Table 2. (continued) Radionuclide
Substance
E (mSv/MBq)
75Se 75Se
1-selenomethionine Selenium-labelled bile acid ( S e H C A T )
2.5 E + 00 6.6E 01
76Br v7Br 82 Br vvBr
Bromide Bromide Bromide Bromospiperone
2.8 E - - 0 1 7.7 E -- 02 4.0 E -- 01 8.5 E -- 02
81 ~ K r
Krypton
9.5 E -- 04
81Rb S2Rb SgRb 86Rb 81Rb
Rubidium Rubidium Rubidium Rubidium Rb-labelled d e n a t u r e d erythrocytes
2.8 E - 02 3.4 E - 03 2.8 E + 00 3.0 E + 00 1.4E-01
SSSr 8 VmSr 89Sr
Strontium Strontium Strontium
7.9E 01 6.4 E - 03 3.1 E + 00
99mTc
99mTC 99mTC 99mTC 99mTc 99mTC
Tc-labelled a l b u m i n (HSA) Tc-labelled citrate c o m p l e x Tc-labelled large colloids Tc-labelled small colloids Tc-DMSA Tc-DTPA Tc-labelled p l a s m i n Tc-gluconate, g l u c o h e p t o n a t e Tc-labelled H M P A O a Tc-penicillamine Pertechnetate Pertechnetate (blocking a g e n t given) P e r t e c h n e t a t e (oral a d m i n i s t r a t i o n , no blocking) Tc-labelled I D A derivatives Tc-labelled fibrinogen Tc-labelled erythrocytes Tc-labelled d e n a t u r e d e r y t h r o c y t e s Tc-labelled p h o s p h a t e s a n d p h o s p h o n a t e s Tc-labelled aerosols ( s u b s t a n c e s with fast clearance) Tc-labelled aerosols (substances with slow clearance) Tc-labelled h e p a r i n Tc-labelled M A G 3 " Tc-labelled m a c r o a g g r e g a t e d a l b u m i n Tc-labelled M I B I (rest)" Tc-labelled M I B I (exercise) a Tc-labelled n o n - a b s o r b a b l e m a r k e r s (fluids) Tc-labelled n o n - a b s o r b a b l e m a r k e r s (solids) Tc-labelled a l b u m i n m i c r o s p h e r e s Tc-labelled platelets ( t h r o m b o c y t e s ) Tc-labelled white blood cells (leucocytes)
8.8E 03 6.1 E 03 9.2E--03 9.7 E - 03 8.7 E - 03 5.2 E - 03 9.8 E - 03 5.4 E - 03 9.2E 03 7.3 E -- 03 1.2 E - - 02 4.7 E - - 0 3 1.4 E - 02 1.5 E - - 0 2 9.1E 03 9.8 E - - 0 3 2.3 E - - 0 2 5.8 E - - 0 3 6.1 E - 03 1.4 E - 02 7.2 E - 03 7.2 E - 03 1.1 E - - 0 2 8.5 E - - 0 3 7.5 E - - 0 3 2.0 E -- 02 2.2 E -- 02 1.0E--02 1.6 E - 02 1.4 E - - 0 2
lllIn 113rain t 13rain 11 t In 113rain 1 ~ In 111in t 13rain ~3rain ~~In 11 In 113~in t ~3r, i n
Indium Indium I n d i u m h y d r o x i d e (colloidal) In-DTPA In-DTPA In-aerosols (substances with fast clearance) In-aerosols (substances with slow clearance) In-aerosols (substances with fast clearance) I n - a e r o s o l s (substances with slow clearance) In-labelled n o n - a b s o r b a b l e m a r k e r s (fluids) In-labelled n o n - a b s o r b a b l e m a r k e r s (solids) In-labelled n o n - a b s o r b a b l e m a r k e r s (fluids) In-labelled n o n - a b s o r b a b l e m a r k e r s (solids)
2.1E 01 1.0E--02 1.1 E -- 02 2.1 E -- 02 1.1 E 02 2.5 E -- 02 2.4 E 01 1.6 E -- 02 2.5 E - - 02 3.1 E -- 01 3.2 E - 01 2.0 E - 02 2.9 E -- 02
99mTc 99mTc 99mTc
99mTC 99roTe 99roTe 99mTC 99mTc
99mTC 99mTC 99mTC 99mTc 99roTe 99myc 99mTC 99myc 99~Tc 99mTc
99myc 99mTC 99mTc 99mTC 99rnTc 99mTc
937
Table 2. (continued) Radionuclide
Substance
E (mSv/MBq)
111 In 11 l i n 111In
In-labelled platelets (thrombocytes) In-labelled white blood cells (leucocytes) In-labelled bleomycin
5.2 E - 01 4.7 E - 01 1.0 E - 01
123I 123I 124I 124I 125I ~zsI 131I 311 1231 z3I 125i 1311 123I 2sI 131I 1311 125I 125I t 311 3~I t23I 131I 1231 12 s I 13 t I 1251 t 2sI 1311 12 s I 1311 12s I 1311 1251 131i 1251 311 t 251 1311 1231 1311 1231 1a 11
Iodide (thyroid blocked, uptake 0%) Iodide (thyroid uptake 35%) Iodide (thyroid blocked, uptake 0%) Iodide (thyroid uptake 35 %) Iodide (thyroid blocked, uptake 0%) Iodide (thyroid uptake 35 %) Iodide (thyroid blocked, uptake 0%) Iodide (thyroid uptake 35 %) I o d o a m p h e t a m i n e (IMP) Iodine-labelled flbrinogen Iodine-labelled fibrinogen Iodine-labelled fibrinogen Iodine-labelled albumin (HSA) Iodine-labelled albumin (HSA) Iodine-labelled albumin (HSA) Iodine-labelled m a c r o a g g r e g a t e d albumin (MAA) Iodine-labelled n o n - a b s o r b a b l e markers (fluids) Iodine-labelled n o n - a b s o r b a b l e markers (solids) Iodine-labelled n o n - a b s o r b a b l e markers (fluids) Iodine-labelled n o n - a b s o r b a b l e markers (solids) Iodine-labelled microaggregated albumin (MIAA) Iodine-labelled microaggregated albumin (MIAA) Hippuran Hippuran Hippuran Iodo-antipyrine Iodo-antipyrine Iothalamata Iodomethyl- 19-norcholesterol (NP 59) Iodinated polyvinylpyrrolidone (PVP) Iodinated polyvinylpyrrolidone (PVP) Thyroxine (T4) Thyroxine (T4) Triiodothyronine (T3) Triiodothyronine (T 3) Reverse triiodothyronine (rTa) Reverse triiodothyronine (rT3) Diiodothyronine Diiodothyronine Metaiodobenzylguanidine (MIBG) Metaiodobenzylguanidine (MIBG) Sodium rose bengal Sodium rose bengal
1.1 E - 0 2 2.2E-01 9.5E-02 1.5 E + 01 9.1 E - 0 3 1.4 E + 01 6.1 E - 0 2 2.4 E + 01 2.7 E - 02 2.9 E - 02 1.1 E - 01 5.6 E - 01 2.7E-02 3.1 E - 01 8.2E-01 4.5 E - 01 1.7 E - 0 1 1.7 E - 01 1.2 E + 00 1.2 E + 00 1.8 E - 0 2 2.2 E - 01 1.2 E - 02 7.7 E -- 03 5.3 E -- 02 6.7 E - 02 1.0 E - 02 7.2 E - 03 1.8 E + 00 6.5 E - 01 6.0 E - 01 1.0 E - 01 4.4 E - 01 4.7 E - 02 3.0 E -- 01 3.7 E - 02 2.5 E - 01 3.6 E -- 02 2.5 E - 01 1.4 E - 02 1.4 E - 01 5.9 E - 02 1.1 E + 00
127Xe 133Xe 127Xe 127Xe 33Xe 133Xe
Xenon-gas Xenon-gas Xenon-gas Xenon-gas Xenon-gas Xenon-gas
1.3 E - 0 4 1.8 E - 04 7.1 E - 04 1.1 E - 03 7.3 E - 04 1.1 E - 03
129Cs 130Cs 31Cs t 34mCs
Caesium Caesium Caesium Caesium
4.9 E - 02 3.4 E - 03 5.0E-02 6.7 E - 03
aa 1Ba 133tuBa 135tuBa
Barium Barium Barium
5.0 E - 01 4.7E--01 3.4 E -- 01
311
(single inhalation or i.v. inj., 30-s breath-hold) (single inhalation or i.v. inj., 30-s breath-hold) (rebreathing for 5 rain) (rebreathing for 10 min) (rebreathing for 5 rain) (rebreathing for 10 min)
938 Table 2. (continued) Radionuclide
Substance
E (mSv/MBq)
131Ba 131Ba
Ba-labelled non-absorbable markers (fluids) Ba-labelled non-absorbable markers (solids)
4.9 E - 01 5.1 E - 01
t4°La
La-DTPA
1.5 E - 0 1
169yb
Yb-DTPA
3.6 E - 02
Gold colloid
1.1 E + 00
t97Hg 197Hg 197Hg 2°3Hg
9SAu
Mercury chloride Bromo-mercuri-hydroxypropane (BMHP) Chlormerodrin Chlormerodrin
1.4E-01 1.4 E - 01 8.7 E - 02 1.1 E + 00
2°iT1
Thallium
2.3 E - 01
" Substance not included in ICRP 53
E HE
+ v . _
All ICRP 53
Tc-9'9m
Iodine
Fig. 1. Box-plots of the quotient between the numerical value for the "effective dose", E, calculated with weighting factors according to ICRP publication 60 (1991), and the "effective dose equivalent", He, calculated according to ICRP publication 26 (1977). The line in the shadowed box marks the median value, and the central 50% of the substances are contained within the box. Values falling below the 10th percentile or exceeding the 90th percentile are separately marked for 99mTc-MAG3 is 12% lower. The explanation for these reductions is the different m e t h o d of weighing the " r e m a i n d e r " , where for the old effective dose a weighting factor of 0.06 was given to each of the five m o s t exposed organs. The numerical values for iodide and some orally administered radiopharmaceuticals have increased: those for t23I-, 125I- a n d 131I-iodide have increased by 6 0 % - 7 0 % for a p r e s u m e d t h y r o i d u p t a k e exceeding 10%. There has also been a significant increase for 131I-norcholesterol. These increases m a y be attributed to a higher weighting factor for the t h y r o i d and for the walls of the gastrointestinal tract, respectively. Thus the numerical value of the weighted sum of organ doses has c h a n g e d marginally, even if the change in o r g a n weighting factors has been considerable. This indicates a high degree of robustness of the effective dose values. The estimate of the risk for radiation-induced fatal cancer has, however, increased considerably in the period 1977-1991, f r o m 0.0125 S v - 1 to 0.04 S v - 1 for a p o p u l a -
tion of workers ( I C R P 1991). F o r the total p o p u l a t i o n the risk is estimated to be 0.05 Sv-1. The main reason for this increase is that the "relative m o d e l " for extrapolating the risk into the future ( N A S 1990) is n o w believed to be the m o s t realistic one for m o s t situations. A second reason is the revised dose estimates for the A - b o m b survivors in H i r o s h i m a and Nagasaki. So, in spite of a reduction in the numerical values of the effective dose, due to m o r e realistic o r g a n weighting factors the estimated risk for fatal cancer has m o r e than doubled. It should be a d d e d that, a l t h o u g h the I C R P publication 60 values are used as the basis for current scientific work, the d a t a have yet to be a d o p t e d in national legislation, and so official figures m a y differ from those given in this paper.
References
Cristy M, Eckerman KF (1987) Specific absorbed fractions of energy at various ages from internal photon sources. Report ORNL/ TM-8381/V1 V7. Oak Ridge National Laboratory ENSDF (1983) Evaluated nuclear structure data file, edited and maintained by the National Nuclear Data Center, Brookhaven National Laboratory, on behalf of the International Network for Nuclear Structure Data Evaluation (August 1983). Summary of file contents and published documentation may be found on page iii on any issue of Nuclear Data Sheets ICRP publication 26 (1977) Recomendations of the ICRP. Pergamon, Oxford ICRP publication 52 (1987) Protection of the patient in nuclear medicine. Pergamon, Oxford ICRP publication 53 (1988) Radiation dose to patients from radiopharmaceuticals. Pergamon, Oxford ICRP publication 60 (1991) 1990 recommendations of the international commission on radiological protection. Pergamon, Oxford Johansson L, Mattsson S, Nosslin B (1984) Effective dose equivalent from radiopharmaceuticals. Eur J Nucl Med 9:485~489 NAS (1990) Health effects of exposure to low levels of ionizing radiation. BEIR V report. National Academy of Sciences. National Academy Press, Washington D.C.
