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Radiation dose to the human body from intravenously administered 75Se-sodium selenite

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The dose of radiation to the human body and some of its organs after intravenous administration of 75Se-sodium selenite for diagnostic purposes has been calculated on the basis of followup of 26 patients for as long as 517 days with measurements of: 1. The retention of 75Se in the whole body. 2. The retention of 75Se in the blood, liver, kidneys, ovaries, testicles, and hair. 3. The excretion of 75Se in urine and feces. Whole-body counting and profile scanning were done on the patients and samples of blood from different organs, urine, and feces were measured for radioactivity. The dose of radiation received was calculated for an average patient of 70 kg. These doses were found to be slightly higher than previously reported on a smaller number of patients and with a shorter follow-up. They were slightly lower than those from 75Se-methionine to the whole body but higher to the liver and kidneys. The margin of error in this investigation was estimated to be about 20% for the whole-body dose and probably higher for different organs, mostly due to the poorly known rate of retention of selenite in different organs.
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The dose of radiation to the human body and
some of its organs after intravenous administra
tion of “Se-sodium selenite for diagnostic per
poses has been calculoted on the basis of fol
lowup of 26 patients for as long as 51 7 days
with measurements of:
1. The retention of 75Sein the whole body.
2. The retention of “Sein the blood, liver,
kidneys, ovaries, testicles, and hair.
3. The excretion of 75Se in urine and feces
Whole-body counting and profile scanning
were done on the patients and samples of blood
Irom differentorgans,urine,andfeceswere
measured for radioactivity The dose of radio
tion received was calculated for an average pa
tient of 70 kg. These doses were found to be
slightly higher than previously reported on a
smaller number of patients and with a shorter
followup. They were slightly lower than those
from 75Se-methionine to the whole body but
higher to the liver and kidneys. The margin of
error in this investigation was estimated to be
about 20% for the whole-body dose and prob
ably higher for different organs, mostly due to
the poorly known rate of retention of selenite in
different organs.
Both the usefulness and the limitations of T5Se
sodium selenite for demonstration of malignant tu
mors have been previously demonstrated (1—5).
Radioactive selenium is a relatively cheap material,
emits gamma rays suitable for detection, and has a
relatively good tumor specificity; 28 :25 :7 :5 :1 rela
tive concentration was experimentally obtained in
kidney:liver: tumor: heart :muscle of hamsters (6).
There are two main limitations for its use in tumor
detection : (A) lesions less than 2 cm in diameter
are usually not visualized due to the limited resolv
ing power of the equipment and (B) a relatively high
dose of radiation to the body due to selenium's long
physical and biologic half-life.
Selenium is a normal metabolite in human nutri
tion. Both selenium toxicity and deficiency are known
in animals. No deficiency is known in humans and
toxicity in humans occurs at much higher doses than
those used in nuclear medicine. The mechanism of
uptake in tissues is not known. It is excreted in urine
and feces. Previous estimates of the radiation dose
to the body and its vital organs are uncertain due
mainly to the small number of observations and
short time of followup. Cavalieri (7) estimated the
radiation dose to the whole body after intravenous
administration of T5Seto be 4 mrads/@Ci injected.
The radiation dose after their standard diagnostic
administration of 400 pCi of T5Sewas 1.1 rads to
the whole body, 4.8 rads to the liver, and 6.1 rads
to the kidney. Nordman (8) estimated slightly higher
doses. Apparently no attempt has been made to esti
mate the dose of radiation to the gonads.
The aim of this study has been to estimate the
dose of radiation to the whole human body and some
of the more important organs from the diagnostically
administered radioactive selenite on the basis of dose
measurements on a relatively large number of pa
tients with long followup.
MATERIALS AND METHODS
Twenty-six patients who had received radioactive
sodium selenite (T5Se) for diagnostic purpose were
studied. The youngest patient was 2 1, the oldest 81
years, the mean age being 52.8 years.
The dose injected was 400 @.cCiof 75Sein all pa
tients. They were followed for up to S 17 days with
measurements of retention and distribution of so
dium selenite. All patients voluntarily agreed to the
Received Jan. 20, 1975; revision accepted April 10, 1975.
For reprints contact: Berta Jereb, Isotope Dept., Radium
hemmet, Karolinska Hospital, 5-10401 Stockholm, Sweden.
846 JOURNAL OF NUCLEAR MEDICINE
RADIATION DOSE TO THE HUMAN
BODY FROM INTRAVENOUSLY
ADM I N ISTE RED 75SE—SODI U M SE LEN ITE
Marlan Jereb, Roif Falk, Berta Jereb, and Christer Lindhe
Karolinska Hospital and State Institute for Radiation Protection, Stockholm, Sweden
200 300 400 500
RADIOCHEMISTRY AND RADIOPHARMACY
procedures involved. The following factors were
measured : (A) retention of 75Sein the whole body
and in the blood; (B) distribution of 75Se, by way
of dose measurements on tissue specimens obtained
at surgery or autopsy, scintigrams of the whole body,
and profile studies of the whole body; and (C) excre
tion of 75Se measured in urine and feces.
The dose of radiation to the whole body was cal
culated on the basis of data obtained by the meas
urement of the retention of T5Se in the whole body.
The radiation dose to the liver, the kidneys, the
gonads, and the bone marrow was estimated on the
basis of the retention of the 75Se in the body and
its distribution within these organs. Reliable reten
tion curves for each of these organs could not be
obtained due to the small number of patients avail
able for these studies. They were assumed for the
purpose of dose estimation to be roughly parallel to
the whole-body retention curve.
Whole-body retention measurements. Whole-body
retention measurements were performed in 26 pa
tients on two of the Institute's whole-body counters
(9) ; an ionization chamber was used when the total
amount of 75Se was more than about 5 MCi; a whole
body scanner was used with lower activities. Fur
thermore, measurements of profile were done on the
Radiumhemmet's LKB-scanner in 16 patients.
The measurements of the blood. The 75Secontents
in 54 blood samples from 15 patients were measured
on a S in. X 4 in. Na! crystal. The smallest detected
quantity was 0.0015 % of the given dose per liter
of blood (3 % over the background) in a 10-mi sam
pie and 10 mm counting time.
The measurements of tissue (organ) specimens.
These measurements were done in the same manner
as those of the blood. ICRP II (10) data were used
for calculation of the 75Se retention in organs. Whole
body scintigraphy was done on only two patients 27
days after the administration of T5Se in both.
The measurements of 75Se in urine and feces.
Measurements of T5Se in urine and feces were done
on six patients on the adjusted whole-body scanner.
The total quantity excreted within 24 hr was meas
ured with the counting time chosen so that the sta
tistical margin of error was less than I %.
The calculation of the radiation dose to the whole
body and some vital organs. This calculation was
done following the principle described by Loevinger
and Berman ( I I ) . The radiation dose to the liver has
been calculated as the sum of the doses from the
accumulated activities in the liver, the kidneys, and
the rest of the body (the latter under the assumption
of equal distribution) . The dose to the whole body
has been calculated both (A) under the assumption
100 200 300 400 500
DAYS
I
FIG. 1. Retentionof intravenouslyadministered ThSe@sodium
selenite in whole body. Corrected for physical decay.
20
10-
DAYS
FIG. 2. Retentionof intravenouslyadministered @Se-sodium
selenite in blood. Corrected for physical decay.
of equal distribution of radioactivity throughout the
body and (B) taking into account the higher ac
cumulation of radioactivity in the liver and the kid
neys and assuming its equal distribution throughout
the rest of the body. The radiation dose to the blood
and to the bone marrow has been estimated by add
ing the dose from the nonpenetrating radiation from
blood and bone marrow to the average dose through
out the body from penetrating radiation.
RESULTS
Accumulation and retention of @@Sein the human
body and some of its organs. Figure 1 shows the
measured retention in the whole body corrected for
physical decay.
The retention rate of T5Se in the whole body has
been approximated by two exponential terms. About
12% of the administered amount is excreted within
the first 24 hr. Thereafter, about 40% is excreted
with a biologic half-life of about 20 days and about
48% with a biologic half-life of approximately 115
days.
Figure 2 shows the measured retention of @@Sein
the blood in percent of administered dose per liter
of blood after correction for physical decay.
Volume 16,Number 9 847
.-Percentage
of
adminstered @Se
@ —@----.-——.
Per WholePercentage
dose
retainedinOrgangram organwhole body
0.0033 9.90 11.4
.Percentage
of
administered @Se
—--—-@
Per WholePercentagedose
retainedinOrgangram organwhole body
0.137 3.4
JEREB, FALK, JEREB, AND LINDHE
Both profile and organ measurements showed the
highest concentration of 75Se in the liver and the
kidneys. Table 3 shows the excretion of 75Sein urine
and feces.
The rate of excretion has also been calculated with
the assumption that the whole-body retention follows
the retention equation. The table shows relatively
good correlation of the measured and calculated
data.
Dose measurements. The fraction of the adminis
tered amount of radioactivity in the different organs
was calculated on the basis of the profile measure
ments and measurements of tissue specimens. Table
4 shows the doses from 1 @cCiT5Se intravenously
administered as sodium selenite.
The accumulation of radioactivity in the gonads
was no higher than in the body as@a whole. There
was relatively little accumulation in the bone mar
row. Most of the 75Se accumulated in the liver and
kidneys with the amount in the liver diminishing
faster than that in the rest of the body. A relatively
high accumulation was found in the hair a long time
after administration. The excretion was mostly in
the urine and feces, the former dominating during
the first month.
DISCUSSION
The margin of error. The margin of error was esti
mated on the basis of the calibration procedures to
be below 10% in the retention measurements of
T5Sein the whole body and in the blood. It was esti
mated to be below 3 % during the first month when
ever measurements could be performed within 24
hr of the administration of the@ Some circumstances contributing to the error in
estimating the radiation dose from 75Se were: (A)
the calculations were performed assuming a homo
geneous distribution of the 75Se throughout an or
gan; (B) a mathematical human model, 70 kg in
weight with “standardsize―organs, was used for the
calculations of the radiation dose to the whole body;
(C) unknown retention curves in the different or
gans had to be estimated from tissue specimens from
sick patients with possibly altered metabolism of
selenium; and (D) the magnitude of the fraction ex
creted with the long half-life of I I 5 days is a bio
logic parameter with apparently rather wide mdi
vidual variation.
The excretion through the lungs of 75Sehas been
investigated before (8) and found to be practically
negligible. It was therefore not investigated here.
The retention of 75Se in the tumor tissue is not
relevant to the consideration of the radiation dose
to the human body and different organs, since in the
TABLE 1. RETENTION OF 75Se IN DIFFERENT
ORGANS*
Bone marrow
Blood (calculated
values) 0.0033
Liver 0.014
Lungs 0.0056
Kidneys 0.034
Testicles 0.0013
S Twenty-four hours after
(whole-body retention = 87°!.).
17.9
23.8
5.6
10.2
0.052
20.6
27.3
6.4
11.7
0.060
intravenous administration
TABLE 2. RETENTION OF 75Se IN DIFFERENT
ORGANS*
Bone marrow 0.000046
Blood(calculated
values) 0.000067 0.362 9.0
Hair 0.00068 0.068 1.7
Liver 0.000308 0.524 13.1
Abdominal lymph
nodes 0.000118 0.047 1.2
Kidneys 0.000453 0.136 3.4
Ovaries 0.0001 34 0.001 07 0.027
S Four hundred sixteen days after intravenous adminis
tration (whole-body retention = 4°!.).
The retention of the 75Sein the blood can also be
described by a two-phase exponential course with
the biologic half-lives of 5 and 97 days, respectively,
about 80% being excreted with a 5-day biologic
half-life.
Tables I and 2 show the retention of T5Se in dif
ferent organs in two different patients at 1 day and
at 416 days after administration, the retention in
the whole body at that time being 87% and 4%,
respectively, of the administered dose.
Only two whole-body scintigrams were done, both
27 days after the administration of T5Se.Both show
the accumulation of radioactivity in the liver and
kidneys but in no other areas of the body. The bulk
of the tumor was removed in both patients after
administration of T5Se and before the scintigrams
were done.
Profile measurements showed the activity in the
region of the liver to diminish faster than in other
areas. This was corroborated to some degree by the
organ measurements.
848 JOURNAL OF NUCLEAR MEDICINE
TABLE 3. EXCRETION OF
Dailyexcretion in percent of administereddose
Patient No.Days after
administrationcorrected
for physical decayCalculated excretion
TotalUrineFecesTotal12110.521.401.921.2328300.331310.260.070.330.712620.190.140.330.3629840.160.130.290.256880.100.040.100.24
TABLE4. DOSEOFRADIATION(MILLIRADS)*Radiation
dose inmillirads per microcurie@°SeBoneRadiation
dose from organmarrowBloodLiverKidneys TesticleOvariesWhole
bodyBone
marrow0.84t
RADIOCHEMISTRY AND
Blood
Liver
Kidneys
Testicles
Ovaries
Rest of body
Whole body (homogeneous
distribution)
Summary 6.5 6.5
S From 1 @zCi 7@Se intravenously administered as sodium selenite.
t Nonpenetrating radiation.
@ Penetrating radiation.
0.83t
26.92.80.0060.241.31.1310.0100.140.48
1.5
2.4
5.3 4.6 5.1 4.2 4.6
33 38 6.6 7.0 6.4
5j@ 6.3
long-term survivors most or all of the tumor has
been removed. In addition, the mass of the tumor
being a relatively unknown and changeable quan
tity, its dosimetry would be expected to be extremely
unreliable. Enough data exist (7,8) to the effect that
the accumulation of 75Se in most kinds of malignant
tumors is high and increases relatively fast (with
respect to other organs) during a short period of
time after administration of 75Se.
The radiation doses calculated in this study are
somewhat higher than those from some previous
studies. However, our calculations for the dose to
the liver and the kidneys are also based only on data
from two patients and are not reliable.
Compared with the radioactive selenomethionine
(with T5Se) , also used for detection of malignant
tumors, the sodium selenite is being excreted some
what faster ( 12) resulting in a lower dose of radia
tion to the whole body. Due to the difference in the
metabolism, however, the dose to the liver and kid
neys is slightly higher from T5Se-sodiumselenite than
from 75Se-selenomethionine.
Technetiuni-99m-pertechnetate, probably the most
widely used diagnostic radioactive isotope at the
present, gives a radiation dose to the whole body of
only 10—20mrads/mCi, i.e., at least 30 times less
than that from 75Se.
REFERENCES
1. BAPTISTA AM: Positive gammagraphy of tumors with
S@3.Distinction ot cancer from benign hepatic tumors. In
Medical Radioisotope Scintigraphy, Vienna, IAEA, 1972
2. ESTEBAN J, LASA D, PEREZ-MODREGO S: Detection of
cartilaginous tumors with Selenium 75. Radiology 85 : 149—
152,1965
3. ESTEBAN J, VAZQUEZ R, FOMBELLIDA JC, et al: Posi
tive diagnosis of tumors with 75-Se-selenite. In Medical Ra
dioisotope Scintigraphy, Vienna, IAEA, 1972
4. JEREB M, UNGE B, JEREB B, et al: Demonstration of
malignant tumors in the lungs and mediastinum by means of
849
Volume 16,Number9
75Se THROUGH URINE AND FECES AFTER INTRAVENOUS
ADMINISTRATION
JEREB, FALK, JEREB, AND
9. FALK R, MAW A, SWEDJEMARKGA: Whole-body
measurement techniques at the Swedish National Institute
of Radiation Protection. Acta. Radio! [Suppi] 310: 94—113,
1971
10. ICRP Publication 2: Recommendations of the Inter
national Commission on Radiological Protection, London,
Pergamon Press, 1959
1 1 . LOEVINGER R, BERMAN M : A schema for absorbed
dose calculations for biologically distributed radionuclides.
MIRD Pamphlet No 1, Suppl No 1, 7—14,1968
12. LATHROP KA, JOHNSTON RE, BLAU M, et al: Radia
tion dose to humans from T5Se-L-SelenomethiOntfle.MIRD
Pamphlet No 9, 1 Nuci Med 13 : Suppl No 6, 10—17, 1972
radionuclear (75 Se) scintigraphy. Scand I Respir Dis 54:
282—289,1973
5. RAY GR, DEGRAZIA JA, CAVALIER! R: @Se-selenite as
a tumor specific bone scanning agent. I Nucl Med 11 : 354—
355, 1970
6. WENZEL M, OTTO R, RIEHLE I : Der Einbau von @‘Se
nach Applikation von radioaktivem Natriumselenit in Nor
malgewebe und in Tumoren in-vitro und in-vivo. mt J App!
RadiatIsot22:361—369,1971
7. CAvALIER! RR, Scorr KG, SAIRENJI E: Selenite (7@Se)
as a tumor-localizing agent in man. J Nuci Med 7: 197—
208, 1966
8. NORDMANE: 75 Se-Sodium selenite scintigraphy in
diagnosis of tumors. Acta Radio! [Suppfl 340: 1974
850 JOURNAL OF NUCLEAR MEDICINE
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dionuclide Procedures in the Detection of Neoplasms; Radioimmunoassay; Cardiovascular Nuclear Medicine;
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... ), bovine (Campo et al. 1966), sheep (Muth et al. 1967), Escherichia coli (Tuve & Williams 1961), mumps virus (Jensik & Northrop 1971) and other living species. In humans, the application of 75 Se was mostly limited to cancer studies using this radiotracer as tumor marker in general (Cavalieri et al. 1966) and for the identification of neuroblastoma (D'Angio et al. 1969), but the radionuclide was also used in studies on selenium metabolism (Ben-Parath et al. 1968, Jereb et al. 1975). The use of stable selenium isotopes allowed a more intensive research with human subjects (Janghorbani et al. 1981, Janghorbani et al. 1982, Veillon et al. 1990). ...
... The radionuclide 75 Se was used for in vivo experiments in rats (McConnell 1941, McConnell et al. 1959), dogs (McConnell & Cooper 1950, McConnell & Van Loon 1955, McConnell & Wabnitz 1957), mice (Anghileri 1966, Hansson & Jacobsson 1966), bovine (Campo et al. 1966), sheep (Muth et al. 1967), Escherichia coli (Tuve & Williams 1961), mumps virus (Jensik & Northrop 1971) and other living species. In humans, the application of 75 Se was mostly limited to cancer studies using this radiotracer as tumor marker in general (Cavalieri et al. 1966) and for the identification of neuroblastoma (D'Angio et al. 1969), but the radionuclide was also used in studies on selenium metabolism (Ben-Parath et al. 1968, Jereb et al. 1975). The use of stable selenium isotopes allowed a more intensive research with human subjects (Janghorbani et al. 1981, Janghorbani et al. 1982, Veillon et al. 1990). ...
... 75 Se is used in high activity brachytherapy (Weeks and Schulz 1986), assessment of pancreatic exocrine function (Goriya et al. 1974, Denisov 1986, study of bile acids and evaluation of illeal function (Ferraris et al. 1986, Soundy 1982, Amaral 1985, industrial radiography (Thiele 1995, NAC Annual Report 1991 and as a tracer in the assessment of chemical, biochemical, biophysical processes, metabolic researches and agricultural studies. 73 Se is used in pancreas scanning (Agnew 1976), hyperthyroidism diagnosis (Amersham International PLC 1990), adrenal scanning (Hawkins et al. 1980), tumor detection (Hara et al. 1973, Jereb 1975, Paterson 1976), detection of brain dopamine receptors (Sadek et al. 1988), parathyroid tumor detection (Amersham International PLC 1990) and detection of brain blood flow (Kung and Blau 1980). These radioisotopes were selected to be produced in the country according to their wide range of applications. ...
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Inorganic selenium (Se) salts (selenite and selenate oxyanions) and the organic selenoamino acids (selenomethionine and seleniferous grains) are teratogenic and embryolethal in domestic and wild birds. Selenium bioaccumulation has been held responsible for reproductive failure among waterfowl at the Kesterson Reservoir (California), the Ouray and Stewart Lake Wildlife Refuges (Utah), and the Carson Sink (Nevada). Anecdotal field and controlled laboratory reports have implicated Se exposure in mammalian embryotoxicity (including human), but developmental toxicity studies in hamsters failed to demonstrate an adverse response, except at maternally toxic doses (Ferm et al., Reprod. Toxicol., in press). Uptake, distribution, and elimination of Se after a single bolus equimolar dose (60 mumol/kg) of selenate or selenomethionine by oral or intravenous administration were compared using day 8 pregnant hamsters. Intravenous selenate was eliminated ten times more rapidly from maternal plasma than oral selenate, but concentrated in liver, kidney, and placenta to the same degree. Intravenous (iv) L-selenomethionine achieved lower maximum circulating total [Se], but it was eliminated more slowly than iv selenate. Larger areas under the plasma and peripheral tissue [Se]:time curve (AUC) after oral or parenteral selenomethionine than after equimolar selenate were consistent with previous studies in rodents and in humans. Embryonic [Se] plateaued at 3 nmol/g after selenate, but embryonic [Se] after selenomethionine continued to accumulate (80 nmol/g) as gestation progressed. The lack of a teratogenic response in hamsters at doses of either selenate or selenomethionine less than those associated with maternal intoxication cannot be attributed to lack of Se accumulation in early embryonic and placental tissue.
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A 45 d metabolic study was carried out in four young adult male North American residents consuming a controlled diet based on an amino acid mixture. During the initial 10 d, total daily selenium intake was adjusted to 107.7 (SE 0.1) microgram/d, which was reduced to 11.4 (SE 0.1) microgram/d for the remaining 35 d. Two doses of a stable isotope (74SeO3(2-)) were administered orally in the post-absorptive state on days 4 and 39 of the study. Se balance (faecal + urinary excretion) as well as stable isotope excretion studies were carried out for the entire 45 d period; blood plasma and erythrocyte Se concentrations were also monitored. Plasma Se concentrations (microgram/ml) fell progressively from the initial value of 0.132 (SE 0.007) to 0.083 (SE 0.008) at the end of the study. The erythrocyte concentrations of Se did not vary in a consistent manner (average value for the entire study 0.147 (SE 0.002) microgram/ml). Faecal excretion of unenriched Se decreased from 66 (SE 6) microgram/d for days 1-10 to 10.2 (SE 0.8) microgram/d for days 14-40. Mean urinary excretions of the unenriched Se were 43.9 (SE 2.8) microgram/d (days 1-10) and 26.9 (SE 4.6) microgram/d (days 14-40). Total balance (intake-faecal excretion-urinary excretion) for unenriched Se was (microgram/d):-18 (SE 7) days 10-19, -17 (SE 2) days 19-39, -5 (SE 1) days 38-45. Fractional absorption of the ingested label was 0.529 (SE 0.032) and 0.542 (SE 0.038) for the Se-adequate and Se-restricted phases of the study. However, urinary excretion of the absorbed label was reduced from 6.57 (SE 0.73)% for day 1 of the Se-adequate phase to only 3.32 (SE 0.26)% for day 1 of the Se-restricted phase. Similar observations were also made for day 7 of each phase. These findings indicate that immediate contribution of ingested Se to the urinary Se pool is small.
Detection of cartilaginous tumors with Selenium 75
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Posi tive diagnosis of tumors with 75-Se-selenite
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ESTEBAN J, VAZQUEZ R, FOMBELLIDA JC, et al: Posi tive diagnosis of tumors with 75-Se-selenite. In Medical Ra dioisotope Scintigraphy, Vienna, IAEA, 1972
Positive gammagraphy of tumors with S@3. Distinction ot cancer from benign hepatic tumors
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BAPTISTA AM: Positive gammagraphy of tumors with S@3. Distinction ot cancer from benign hepatic tumors. In Medical Radioisotope Scintigraphy, Vienna, IAEA, 1972