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Technetium-99m Dose Calculations: Study on Pertechnetate, Albumin, and Sulfur Colloid, Slides of Communication

A scientific article from the Journal of Nuclear Medicine, published in 1965, discussing internal dose calculations for Technetium-99m. The article covers the pertechnetate ion, technetium-bound serum albumin, and sulfur colloid, providing equations and tables for calculating the integral gamma-ray dose-rate constant, relative intensities of Ka and K@ x-rays, and absorbed doses to various organs. The study aims to understand the energy absorption and distribution of Technetium-99m in the human body.

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JOURNALOF NUCLEARMEDICINE 6:231-251, 1965
Internal Dose Calculation for °°mTc
E. M. Smith, Sc.D.―2
New York
In the second portion of this two part article on UUmTc,internal dose calcu
lations will be made for the pertechnetate ion, for technetium bound serum
albumin and for the sulfur colloid. Internal dose calculations for the pertechne
tate ion will be made for both the oral and intravenous administrations. The
asborbed dose due to the photons of 99@'Tcwill be calculated for both the standard
method (1) using the geometrical factor, and the method recently discussed by
Ellett, Callahan and Brownell (2, 3), using the absorbed fraction. In the first
part of this article the characteristics, potential uses, radiochemical purity and
methods of determining the activity of UUmTcwere discussed (4).
The method of producing technetium bound serum albumin is given by
McAfee, Stern Ct al (5). The method of producing the technetium-sulfur colloid
is given by Richards (6).
CALCULATION OF E@, F AND @yFOR 99mTC
Figure 1 gives the decay scheme for flflmTc. Additional data needed to cal
culate the total local energy deposited per disintegration, @,is found in the
Nuclear Data Sheets (7). The N/L/MN ratios for the relative occurrence of
conversion electrons froni the 0.140 MeV photon is 790/100/30, the ratio of K
conversion electrons for the 0.140 MeV photon to the K conversion of the 0.142
MeV photon is 0.097 and the K/L111 ratio for the relative occurrence of conversion
electrons from the 0.l4fMeV is 2.5. From these data and the internal conversion
coefficient, at 0.095, the number of conversion electrons resulting from internal
conversion of the 0.140 MeV and 0.142 MeV photon can be calculated. Using the
equation presented by Smith et al (8), which is an extension of the treatment by
1U.S. Department of Health, Education, and Welfare Public Health Service, National
Institutes of Health Clinical Center, Department of Radiation Safety, Bethesda, Maryland.
20014.
‘Manuscriptwritten during period of service at the National Institutes of Health. Present
address: Hospital for Special Surgery, Cornell Medical Center, 535 East 70th Street, New
York 21, New York.
231
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JOURNALOF NUCLEARMEDICINE 6:231-251, 1965

Internal Dose Calculation for °°mTc

E. M. Smith, Sc.D.―

New York

In the second portion of this two part article on UUmTc,internal dose calcu lations will be made for the pertechnetate ion, for technetium bound serum albumin and for the sulfur colloid. Internal dose calculations for the pertechne tate ion will be made for both the oral and intravenous administrations. The asborbed dose due to the photons of 99@'Tcwill be calculated for both the standard method (1) using the geometrical factor, and the method recently discussed by Ellett, Callahan and Brownell (2, 3), using the absorbed fraction. In the first part of this article the characteristics, potential uses, radiochemical purity and methods of determining the activity of UUmTcwere discussed (4). The method of producing technetium bound serum albumin is given by McAfee, Stern Ct al (5). The method of producing the technetium-sulfur colloid is given by Richards (6).

CALCULATION OF E@, F AND @yFOR 99mTC Figure 1 gives the decay scheme for flflmTc. Additional data needed to cal culate the total local energy deposited per disintegration, @,is found in the Nuclear Data Sheets (7). The N/L/MN ratios for the relative occurrence of conversion electrons froni the 0.140 MeV photon is 790/100/30, the ratio of K conversion electrons for the 0.140 MeV photon to the K conversion of the 0. MeV photon is 0.097 and the K/L111 ratio for the relative occurrence of conversion electrons from the 0.l4fMeV is 2.5. From these data and the internal conversion

coefficient,at 0.095, the number of conversion electrons resulting from internal

conversion of the 0.140 MeV and 0.142 MeV photon can be calculated. Using the equation presented by Smith et al (8), which is an extension of the treatment by

1U.S. Department of Health, Education, and Welfare Public Health Service, National Institutes of Health Clinical Center, Department of Radiation Safety, Bethesda, Maryland.

‘Manuscriptwritten during period of service at the National Institutes of Health. Present address: Hospital for Special Surgery, Cornell Medical Center, 535 East 70th Street, New York 21, New York. 231

232 E. M. SMITH

Loevinger (1), the energy associated with internal conversion, Ee, which is to be

included in Efl can be calculated.

Ee = fNeK { E@ —WKEK + WK[(Ka@K@) EL11111 + (Ka@K@) EM11 +

+ fNeL - E'y MeV/dis 1.

where E0 = energy associated with internal conversion per disintegration (MeV/dis)

f = fraction of disintegrations that give rise to a photon of energy E'y

@ = total number of conversion electrons,

N0@= NOK + NOL

NOK = number of K conversion electrons arising from a photon of energy E-y per disintegration NeL = number of L,M,N... conversion electrons arising from a photon of energy E'y per disintegration WK = K — fluorescent yield

= relative intensity of Ka x-rays emitted per disintegraticn due to K Ka+Ki internal conversion K@.. -. = relative intensity of K$ x-rays emitted per disintegration due to K internal conversion EK = bonding energy of the K electron EL11111 = average binding energy of the L11 and L111electrons

EM11..111 = average binding energy of the M11 and M111 electrons

The relative intensities of the Ka and K@x-rays may be calculated from Table VlII- of Compton and Allison (9) by setting up simultaneous equations for the ratios of Ka1/Ka, x-rays, K,91/Kfi, x-rays and K@s,/Ka1 x-rays and solving. For oomTc, Ka K@ Ka+K@ = O.8lSandK-+K-- = 0.185.

For Z = 43; WK = 0.76 (10); EK = 0.0211 MeV, EL11111 = 0.0027 MeV and EM11111 = 0.0004 MeV (11).

For the 0.140 MeV photon

N at ________ et 1 + at —1 + 0.095 =

@ then N@ = + 100 + 30) N. = 0.

Photon Energy (E1) (Me V)n

(Corrected for Conversion electrons)1'air@@@'@ (cm')F

% of r0.140 (R-cm2/mc-hr Total

+ 0.142 0.904 2.94X 10@

0.0183 0.067 8.0 X 10@

0.0206 0.014 5.6 X 10@

TOTAL0.

100TABLE

II

@ uimTCPhoton EVALUATION OF FOR

Energy (E@) (MeV)

0.0206n@

_(Corrected for Conversion Electrons)/rads—gm_

( J

\ Ac-hr/%

of

@y0.904 Total

0.22TOTAL0.2729100.

234 E. M. SMITH

increases rapidly in the very low photon energy region. The use of the larger value of F would result in increasing the average gamma-ray exposure-rate, Ry, by 29 per cent whereas the total energy associated with the K x-rays is only 1. per cent of the total photon energy emitted by 9imTc.

EVALUATION OF THE GAMMA-RAY ABSORBED DOSE-RATE Loevinger et al (1) give the classical equations for calculating the average gamma-ray exposure-rate, R'y(t).

@ R@y(t) = i0@ C(t)TP R/hr 4.

Where C(t) is the concentration of the radionuclide in /sc/gm at some moment of time in an organ whose density is p and has an average geometrical factor of @. The average geometrical factor is a complex parameter and relates attenuation of the radiation field by tissue and diminution of the radiation field by the inverse square law. The magnitude of g depends on phantom shape, phantom mass and

TABLE I EVALUATION OF F FOR 99mTc

INTERNAL DOSE CALCULATION FOR OOmTC 235

@ photon energy. The equation for is given by

- @=v@J 1 1 gp (IV cm 5.

. _@LCffr and gp = J @—@—dV cm 6.

In the calculation of g (12), the value used for the effective tissue absorption

coefficient, /.@eff,@50.028 cm ‘which is assumed to be constant. The value used for @teffand the assumption that it is constant is a good approximation for the photon energies emitted by radium, over a limited range of distance upon which @ the values of and gp appearing in the literature are based. For radionuclides which emit low energy photons such as ‘97Hg,i9mTc and ‘99Au,as well as the x-rays eniitted resulting from internal conversion and electron capture processes, /2eff should not be assunied constant. This is true for low energy photons because the Compton effect becomes less important as a mechanism for energy deposition in tissue with decreasing photon energy, and the photoelectric effect becomes increasingly more important as the energy of the photon is degraded. The proba bility of a photoelectric effect occurring is highly dependent upon photon energy as is the Conipton process below 0.1 MeV. @ The other factors which are important in evaluating are the shape of the phantom and mass of the phantom. These two factors will determine the average distance a photon traverses in a phantom, which is a measure of the number of interactions a photon will experience. Each interaction decreases the photon energy and changes the probability for the next interaction, i.e., neff. As will be seen in Table III, the standard method may underestimate the absorbed dose resulting froni low energy photons by as much as 30 per cent due to the assumption of a constant @tLeff. Recently, Ellett, Callahan and Brownell (2, 3) have presented a technique for calculating the gamma-ray absorbed dose using Monte Carlo type calcula tions. In this technique, the actual energy absorbed in the phantom per photon interaction, and the probability of the next interaction is considered, thereby eliminating the difficulties encountered by the standard technique with low energy photons. The fraction of @-y,Eq. 3, absorbed in phantoms of various geometrical shapes and of various masses for different photon energies is determined. The average absorbed dose rate may then be calculated by the equation

@ Ry(t) = C(t)

and evaluating @yfrom Eq. 3 7.

@ Ry(t) = 2.13 C(t) nE(A.F.)E1M rads hr

The absorbed fraction, A.F., is that fraction of the emitted photon energy ab sorbed by a phantom of specified mass and geometry. The A.F. is dependent upon the geometrical shape of the phantom, the mass of the phantom, photon energy and distribution of the radionuclide in the phantom.

INTERNAL DOSE CALCULATION FOR vomTc 237

pharmaceutical will be assumed to be administered intravenously into a 70 kg standard man as defined by the I.C.R.P. Report II (13). The model for the gastrointestinal tract as defined by the I.C.R.P. will be used except for a stomach emptying time of one-half hour rather than one hour. This iiiodel has been ques tioned with regard to the transit times (14) and effective radii (15) of the various segments of the gastrointestinal tract, but in consideration of the short physical half-life of iimTc, the variability of the fecal data and the manner in which the absorbed dose calculations will be performed, the I.C.R.P. model is adequate. The nuclear properties of the radionuclides under consideration are given in Table IV. The average absorbed dose resulting from beta type radiations will be treated by standard techniques (1). For dose calculation purposes, the sum of exponentials will be used to describe the concentration of the radiopharmaceutical as a func tion of time.

@ D$(QD)= 73.8 Co@T@ff 8.

Where Co@ is the initial concentration of the radiopharmaceutical associated with the jth component of the uptake or disappearance curve for a given organ n @@c/gm.The effective half-life of the di component is Teff' in days. It should be remembered that, in many instances, the effective half-life used in dose calcula tions has no physiological significance. Also, Co@ should not be indiscriminately used to calculate pool size. The average absorbed dose resulting from gamma type radiations will be treated, as discussed previously, by the techniques of Ellett et al (2, 3).

D7(@( = 73.8 [@niEi(A.F.) EiM ]ECOJTeffi rads 9.

Where @nE1(A.F.) ElM retains the definition of equation 7, but is evaluated for the organ under consideration. The term @n1E1(A.F.)EiM can he evaluated for the case where the radiopharmaceutical is uniformly distributed in the organ or concentrated and treated as a central point source in the organ. The fornier gives the average gamma-ray absorbed dose and the latter the maximum. The absorbed fraction, A.F., does not include photons scattered back from the surrounding medium (2), therefore the absorbed dose that might result from backscattered photons is not included. This component must be included in the absorbed dose calculation for organs centrally located in the body. For 40 key photons this amounts to an increase in the absorbed dose of 14 per cent, for 80 key photons 28 per cent, for 160 key photons 17 per cent, for 364 key photons 5 per cent and for 662 key photons 4 per cent (3). The total body absorbed dose calculations are based on excretion data, and the traditional assumption that the radiopharmaceutical is uniformly distributed

in the TOTAL body mass. This calculation is usually made and required when a

radiopharmaceutical is being evaluated from a dosimetry point of view, how ever, the significance of this calculation from a biological standpoint is question able. A radiopharmaceutical is rarely, if ever, distributed uniformly throughout

Radionuclide4Physical Half-life (days)E@t

(Me V/dis)@y

/rads/gm@ (

ic-hrTc-99m \

Hg- Hg- Au- Au-1990.

238 E. M. SMITH

the TOTAL body mass, and therefore a low value for the total body absorbed dose is not indicative that one or more essential organs will not receive ten or one hundred or even more timesthe totalbody absorbeddose.In fact,thisisusually the case. For exaiiiple, the kidney absorbed dose for 203Hg Neohydrin is approxi mately 85 times greater than the total body absorbed dose, Table VII. The beta contribution to the gonadal absorbed dose is assunied to be equal to the total body beta absorbed dose unless the actual concentration of the radio pharmaceutical is known in the gonads. In calculating the gamma contribution to the absorbed dose to the female gonads the backscatter correction factor is used. The gamma contribution to the gonadal absorbed dose is based on a uni form distribution of the radiopharmaceutical unless an organ in the vicinity of the gonads concentrates the radiopharmaceutical. Then, the fraction of the activity concentrated in that organ is treated as a central point source in calcu lating this component of the gonadal absorbed dose. It is realized that this ap proach is an approximation, but it is probably as accurate as attempting to fix the coordinates of two organs that may vary their positions with respect to one another, and then to calculate the absorbed dose that one organ receives from the other. The contribution to the female gonadal absorbed dose from urine activity in the bladder and fecal activity in the gastrointestinal tract is adequately handled by treating this activity as a central point source in consideration of the discussion on urinary irradiation of the ovaries by Comas, et al (17) and the dis cussion on fecal irradiation of the ovaries by Maclntyre, et al (18). Calculations for the absorbed dose to specific organs are based on the con centration of the radionuclide in that organ, the geometrical shape and the mass of that organ. Also included in the absorbed dose is the contribution from photons

TABLE IV NUCLEAR PROPERTIES OF RADIONUCLIDES UNDER CONSIDERATION

°Decay schemes used in calculation of E and @yare from the Nuclear Data Sheets, National Research Council, National Aca@emy of Science. °°Calculatedusing equations from reference 8 and E8 calculated using equation from reference 13, and reference 16. tCalculated for an infinite tissue-like medium, i.e., A. F. = 1. IFromSlackandWay, reference10.

Radio-pharmActivity AdminTotal

Body A bsorbed Dose Estimate (rads)Absorbed

Organ―OrganAbsorbedDose to “Critical

Dose (rads)Tc99mO4* Estimate

J Albumin@

Hg Neohydrin@

Hg' Neohydrin@lOmc

375 ,@c

750 @zc

750 @ic0.

0.09U.L.I.t

Blood

Kidney

Kidney0.

38—

240 E. M. SMITH

O9mTc AS THE PERTECHNETATE ION OomTechnetium as the pertechnetate ion, Tc04, was first used by Harper et al (19) for thyroid and brain scintillation scanning. McAfee et al (20) have discussed in detail the technique of brain scanning using Tc04 and the distri bution of Tc04 in man. In their paper, they considered the effect that preadmin istering perchlorate and/or iodide had on the distribution of Tc04 in man as well as the method of administering the radiopharmaceutical. Like iodide, Tc is concentrated by the thyroid, salivary glands and gastric mucosa (21). Pre treating with iodide will block the thyroid, while pretreating with perchiorate will block the thyroid and also decrease the concentration of Tc04 in the gastric mucosa (21). Fifteen to twenty-five percent of the intravenously administered OOmTcactivity is recovered in the first three days in the feces, whereas little if any 1311 as the iodide ion is excreted in the feces. In this respect, Tc04 may differ from iodide in that it is not completely absorbed in the intestines; however, there is the possibility that a fraction of the 99mTc found in the feces may be the result of some metabolic process involving the liver. This inference is based on Mc Afee's data (20) indicating a longer disappearance time for OOmTcin the liver and the high oomTc levels in the liver of mice. Harper (21) has performed studies in man and various animal species to

TABLE VII

COMPARISON OF THE ABSORBED DOSE FROM VARIOUS RADIOPHARMACEUTICALS

USED FOR BRAIN SCANNING

°Intravenousinjection with potassium perchiorate pretreatment. °°Absorbeddose to intestinal mucosa of upper large intestines.

fPretreatmentwith Lugol'ssolution,and the absorbeddose calculatedon basis of

kinetic data from reference 23 and 24. @Absorbeddose calculated on basis of kinetic data from reference 25 and 26.

INTERNAL DOSE CALCULATION FOR °°‘@rc 241

evaluate the factors which control the rate at which Tc04 equilibrates with various body spaces. The blood disappearance curve for an intravenously administered dose of Tc04 is made up of at least two resolvable components. Harper postulates that the fast component (biological half-time of approxi mately 10 minutes) is due to equilibrium with interstitial fluid, and the slow component (biological half-time of approximately 6 hours) is associated with intracellular penetration. The data from human excretion studies carried out by McAfee and Harper are summarized in Table V. Excreta were collected for three days and a laxa tive was given at the beginning of the second or third day. Pretreating the volunteers with iodide had no effect on the rate that OomTc was excreted. Pre treatment with perchiorate had no apparent effect on the excretory pattern of OOmTcwhen it was orally administered; however, there was a 10 percent reduc tion in fecal excretion when OOmTcwas administered intravenously with perchlo rate pretreatment. Approximately 90 percent of the fraction of OOmTcthat is excreted in the urine is excreted in the first 24 hours, and approximately 90 percent or more of the fraction of ovmTc that is excreted in the feces is excreted in the second and third day.

Fig. 1 0.142 MeV

98.6% y@ 0.140MeV

@ 1.4% 98.6% 72 (Internal conversion ratio = 0.095)

0.0 _______ __________L@@@Tc (T4= 2.1 X lO5yr)

________________________99Ru (Stable)

yi 0.002MeV 72 0.140MeV 73 0.142 MeV Fig. 1. Decay scheme of @mTc.

INTERNAL DOSE CALCULATION FOR 99―TC 243

component of the stomach absorbed dose from this activity was calculated using the backscatter factor and the appropriate effective half-life. For the case when the TcO4 is orally administered a 30 minute residence time in the stomach was used, and the activity was assumed to be uniformly distributed in the stomach contents which has a mass of 250 gm ( 13 ). The gastric mucosa is irradiated by the stomach contents under 50 percent geometry (2@-). The effective radius of the stomach is 5 cm which will yield a sphere weigh ing 524 gm from which the absorbed fraction was calculated to determine the gamma component of the absorbed dose. The calculation of the absorbed dose to the upper large intestines ( intes tinal mucosa ) from the activity in the feces was based on the fecal excretion data, Table V, and the model for the gastrointestinal tract as given by the

I.C.R.P. Report II ( 13). The absorbed dose to the intestinal mucosa from the

activity in the feces was calculated in the same way as the absorbed dose to the gastric mucosa was calculated for the 99―Tcresiding in the stomach for 30 min utes. The gamma component of the absorbed dose to the intestinal mucosa was calculated in the same manner as was the gamma component for the stomach absorbed dose except the backscatter factor was not used. The absorbed dose to the thyroid was calculated for a 20 gm gland. Based on Atkin's and Schiffer's data (22), a 3 percent uptake was assumed when Tc04 was intravenously administered, 2.3 percent uptake when orally adminis tered and no uptake when the patient was pretreated with perchiorate. The biological disappearance half-time from the thyroid was taken as 12 hours (22), and instantaneous uptake by the gland was assumed. The gamma component of the absorbed dose to the thyroid from the activity uniformly distributed in the body was calculated as previously discussed.

DISCUSSION In Table VI, the absorbed dose to variousorgans from 10 mc of ovmTc as Tc04 is compared for both oral and intravenous administration, with and without pretreatment with perchiorate. In Table VII, the absorbed dose re ceived from vOmTcis compared to other brain scanning agents such as 1311labeled serum albumin (23,24), 19THg and 203Hg labeled Neohydrin (25, 26). The gamma component of the absorbed dose for these radiopharmaceuticals was cal culated as previously described. The term “criticalorgan― implies that organ which receives the highest absorbed dose, and does not consider the radiosensi tivity or essentialness of the organ. From an absorbed dose standpoint, ovmTc is definitely superior to the other agents evaluated. At present 10 mc of vomTc are administered for a brain scan, this activity may be reduced by as much as a factor of two as soon as more sensitive collimators are used which take advantage of the nuclear properties of O@)mTc.Flarris et a! (27), recently described such a collimator. The absorbed dose to the blood from ‘@‘Ilabeled serum albumin was calcu lated using the levels of activity in plasma and a volume of distribution equiva lent to the blood volume for calculating the beta component of the absorbed dose. It is realized that using the blood volume as the volume of distribution

244 E. M. SMITH

may lead to overestimating thçbeta component of the absorbed dose by as much as a factor of two, since in many regions of the vascular system the particulate radiations will not be completely absorbed in the blood, but will be absorbed in adjacent soft tissue. Use of the above criterion is better than possibly under estimating the beta component of the absorbed dose to blood by a factor of thirteen, i.e. using the total body as the volume of distribution. This is especially true if one uses the blood absorbed dose to reflect the absorbed dose to the hemapoietic system. Ideally one would like to divide the vascular system into two or three sub-systems, assign an effective diameter to each and then calculate an effective blood volume for various electron energies. Absorbed dose estimates should be made at the suborgan level when it is known that a radiopharmaceutical concentrates in an anatomically separate portion of an organ, and the anatomical separation is greater than the range of par tides taken into account by £@.A well-known example of this is the increase in concentration of Neohydrin in the cortex of the kidney as compared to the me dulla (28, 29). The increased concentration of Neohydrin in the cortex of the kidney could double the absorbed dose estimate given in Table VII. The range in the kidney absorbed dose estimate given in Table VII is due to the lack of adequate kinetic data for this radiopharmaceutical.

9ft1@brcLABELEDSERUMALBUMIN

McAfee et al (5) has used 99mTc labeled serum albumin for scintillation scanningof the placentaand other vascularstructures.For placentalscans, mc of vomTc labeled serum albumin is used in comparison to 5 @cof 1311labeled serum albumin (30, 31, 32), for placental localization studies. Placenta scans give the clinician detailed information on the exact location of the placenta, whereas with placental localization studies the clinician must evaluate the location of the placenta from measurements made at ten to twenty arbitrary locations on the abdomen of the mother. Studies carried out by McAfee et a! (5), in pregnant rabbits near term indicated that the tissue distribution of OOmTclabeled serum albumin was similar to 1311 serum labeled albumin. In three normal volunteers, less than 0.5 percent of the injected radioactivity was recovered in either the urine or feces within the first 24 hours after injection. In these volunteers, the initial biological half time in the bloodstream is about six hours and a similar initial biological half-time was found in pregnant women who were administered OomTc labeled serum albumin for placental scans. There is no concentration of 9OmTc when adminis tered as labeled serum albumin in the thyroid, salivary glands or gastric mucosa, when the patient is given 200 mgms of potassium perchiorate one to two hours prior to injection of the radiopharmaceutical. The bodies of two infants (delivered approximately one and four hours fol lowing the injection of 1 mc of 99mTc albumin to the mother) contained 0. percent of the administered dose as determined by external counting and com parison with a phantom. The vvmTc concentration of cord blood was two percent of the maternal blood concentration (5), which is very similar to the values reported for 1311 labeled serum albumin, (30,33). The ratio of 1311 activity in

246 E. M. SMITH

@‘t@―TcSULFUR @OLLOID The S@l@fl1Tcsulfur colloid has been used by Harper et al ( 35 ) , and Atkins Ct a! ( 36 ) , to obtain liver and bone marrow scans. There are many radio pharmaceuticals which permit scintillation scanning of the liver, such as col @ loidal ‘95Au, colloidal ‘““Au,‘‘I aggregated serum albumin ( 37 ) , and Rose Bengal. The first three of these agents are concentrated by the reticuloendo theliai cells of the liver, spleen and red bone marrow, as is the OOmTcsulfur colloid. Edwards et a! ( 38 ) , performed a series of 32 bone marrow scans using both isotopes of colloidal gold as well as heat-treated human serum albumin tagged with ‘@‘I.The disadvantages of the latter radiopharmaceutical are that the metabolized ‘@‘Iproduces a high background for the bone marrow scan and the 131 I that accumulates in the bladder obscures some of the marrow areas. Only the isotopes of colloidal gold yielded satisfactory scans. However, Edwards concluded that the possibility of harmful effects from the radiation absorbed dose from the radioactive colloidal gold years after administration, limits the method to selected patients. The absorbed dose from OomTc is not a limiting factor in bone marrow scanning using the ftOmTcsulfur colloid. The distribution of the 99mTc sulfur colloid in man when administered intravenously appears to be very similar to the distribution of colloidal gold. Root

et al (39), studied the distribution of colloidal ‘98Auin six terminal cancer

patients and roughly estimated that normal liver tissue contains between 60 to 94 per cent of the administered dose, and the spleen and red bone marrow contains approximately 5 to 16 per cent each. Urinary excretion and blood disappearance studies were performed by Atkins et a! (36), in six patients who had received the nOmTc sulfur colloid. These studies indicated that the blood disappearance half-time averaged 2.5 mm with a range of 1.5 mm to 4.4 mm while the 24 hr urinary excretion averaged 3.0per centwith a range of 2.4per centto 3.7per centof the administereddose. The results of these studies are very similar to those of Harper's et a! (35), per formed in mice and dogs. Studies in rabbits, mice and dogs indicate that the body distribution of the colloid is similar to colloidal gold. The particle size of the 99―Tcsulfur colloid in these studies were 500 millimicrons or less. The dis tribution of the colloid in man may be somewhat dependent on particle size, and therefore would effect the absorbed dose calculations. There is less than 3 ,@gof sulfurper ml of the sulfurcolloid(6), and the DomTc activityper @g of sulfur colloid is in the mc/@tg of colloid range. Therefore, a minuscule mass of thesulfurcolloidisadministeredtothepatient.

ASSUMPTIONS AND CONSIDERATIONS The absorbed dose to the liver, spleen and red bone marrow was calculated fora distributionof 90 per cent of the colloidin the liver,5 per cent each in the spleen and red bone marrow with an alternative distribution of 70 per cent in the liver and 15 per cent in the spleen and red bone marrow (39). The colloid was assumed to be instantaneously taken up by these organs, and the effective half-life for the elimination of the colloid from these organs was taken to be equal to the physical half-life. The liver was assumed to be a 1700 gm flat

Radiopharm. and Activity AdminOrganA

(mrads)Frombsorbed Dose Estimate

$ Type RadiationFrom

@yType RadiationTotalTc-99m

Albumin* 1 mc

1-131 Albumin@ 5 @cMaternal

Total Body Maternal Blood Fetal Bloodt

Maternal Total Body Maternal Blood Fetal Bloodt4.

INTERNAL DOSE CALCULATION FOR °°@‘TC 247

ellipsoid, the spleen a 150 gm flat ellipsoid, and the red bone marrow mass was assumed to be 1500 gm and distributed throughout the body (A.F. calculated for a 70 kg ellipsoid) - The length of a flat ellipsoid is four times the thin diam eter, and the thick diameter is twice the thin diameter. The method of calculating the absorbed dose to these organs has already been discussed. Only physical decay was considered in calculating the total body, male and female gonadal absorbed dose. The method of calculating these values using the backscatter factor and the central point source consideration where appro priate has already been discussed.

DISCUSSION

The absorbed dose of oornTc as the ftDmTcsulfur colloid is compared to the absorbed dose received from colloidal 198Au and 1311 aggregated albumin for liver scanning, Table IX, and is compared to the absorbed dose received from colloidal 19MAuand colloidal 199Au for bone marrow scanning, Table X. The absorbed dose for these radiopharmaceuticals was calculated as previously de scribed. The approximate absorbed dose estimates to the liver and total body for 1311 aggregated albumin were based on the kinetic data of Taplin et al (37). The two alternative distributions of the radioactive colloids produce sig nificant changes in the absorbed dose received by the spleen and red bone marrow. The distribution in which only 70 per cent of the colloid was in the liver, and the remaining colloid equally distributed between the spleen and red bone marrow results in a colloid concentration which is higher in the spleen

TABLE VIII COMPARISON OF THE ABSORBED DOSE FROM SOmTC LABELLED SERUM ALBUMIN FOR PLACENTAL SCANNING AND 131J LABELED SERUM ALBUMIN FOR PLACENTAL LOCALIZATION

*Mother pretreated with potassium perchlorate. tCalculationbasedonfetusremaininginuteroindefinitely. SMother pretreated with Lugol's solution.

INTERNAL DOSE CALCULATION FOR OOmTC 249

than in the liver. This could be indicative of a diseased liver. Since nuclear medical procedures are performed to determine whether an organ or an organ system is pathological or normal, due consideration should be given to the absorbed dose for the pathological state. As can be seen from Tables IX and X the absorbed dose to an organ normally not considered to receive a large absorbed dose may in fact be the organ receiving the highest absorbed dose when a possible pathological state exists in the patient. An illustrative example would be an uremic patient who is to have a renal scan with 203Hg Neohydrin. The hepatic uptake of the radiopharmaceutical in this case is greatly in creased (40), resulting in an unexpectedly high absorbed dose to the liver, as compared to the absorbed dose calculated based on the kinetics of Neohydrin for normal individuals.

SUMMARY The total local energy deposited per distintegration, £@for oomTc is 14 key per disintegration. The specific gamma-ray constant, 1', for OvmTc is 0. R-cm2/mc-hr; however, 29 per cent of this value is due to Ka and Kfi x-rays which make up only 1.2 per cent of the total photon energy emitted by OOmTc.Standard methods of calculating the gamma component of the absorbed dose for OomTc using the geometrical factor and r yield results which under estimate the absorbed dose by 16 to 30 per cent compared to calculations based on Monte Carlo techniques which take into account the energy dependence of !Lair and the inflated value of r. The Monte Carlo technique was used in making the absorbed dose estimates in this paper. Absorbed dose estimates were made for oomTc as (a) TcO4 —for brain scanning, as compared to 1311labeled serum albumin and 203Hg and 9THg labeled Neohydrin; (b) oomTc labeled serum albumin for placental scanning, as com pared to 1311labeled serum albumin; and (c) the oOmTc sulfur colloid for liver and bone marrow scanning as compared to colloidal 198Au, colloidal 199Au and 1311 aggregated albumin. Some of the biological problems encountered in calcu lating the absorbed dose are discussed.

ACKNOWLEDGMENTS The author expresses his appreciation to Drs. J. G. McAfee, H. L. Atkins, L. M. Schiffer, P. V. Harper and their coworkers for providing him with excretion and body distribution data, to Dr. G. L. Brownell for allowing the prepublication use of data which has allowed him to apply the absorbed fraction concept to theseabsorbed dose calculationsand to Dr. J.G. McAfee and C. C. Harrisfor their encouragement during the preparation of this paper.

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