International Journal of Applied Radiation and Isotopes, 1975, Vol. 26, pp. 667-670. Pergamon Press. Printed in Northern Ireland

Rapid Estimation of the Radiation Dose to Patients from Radionuclidic Impurities in Eluates from Generators L E L I O O. C O L O M B E T T I Department of Pharmacology, Loyola University Stritch School of Medicine and Nuclear Medicine Division, Michael Rcese Medical Center, Ellis Avenue Chicago, IL. 60616, U.S.A. (Recdved21 ~lrard~ 1975) A method is presented for the estimation of the contribution to patient radiation dose from the radioactive impurities in eluates from generators. The proposed equations involve the dose equivalent per unit of activity, the fraction of the radionuclidic impurity contained in the principal radionuclidic activity and the time lag between milking and administration of the radiopharmacentical to the patient. An example of the values of dose equivalents for some impurities occurring in eluates of 99mTc is presented. INTRODUCTION

neutron activation produced 9gMo have distinctly different types of radioactive impurities. in a wide variety of on-site prepared radio- These impurities are passed along to the 98"Tc pharmaceuticals has created some problems of when it is separated from the parent °gMo. T h e quality control. Chemical purity as well as method of separating the daughter product, also apyrogenicity and sterility are important determines the type and levels of impurities. features in a pharmaceutical product, but " e R e is the principal contaminant found in radiopharmaceuticals have an additional charac- organic extracted 9OraTe(l)while 184Cs was found teristic peculiar to itsc1£ It is important to take by BARRAL et al. as well as by M~INHOLD(m tO into consideration the radionuclidic purity be the main contaminant in generator extracted because with the passage of time, a minor long- pertechnetate. The type and levels of conlived constituent may become the predominant taminants are quite different in sublimed radionuclide present, as it happens for example, 9~'~Tc as well In most cases, a larger number of contamiwith 2°SHg, an impurity found in 197Hg. nants are found in elutes from generators. Particular attention should be given when a short-lived radionuclide is produced from the However, only a few attempts have been made decay of a long-lived parent, as is the case with to assess the radiation dose increments due to the 9~Mo-g~mTc, 97y-sTmSr and 11SSn-llSmIn these impurities, c~v> Although the results of generators. When radiopharmaceuticals l a b d e d these attempts are useful a general mathematical with millicurie amounts of the short-lived formulation is needed that will make it possible daughter products of these generators are to calculate the radiation dose absorbed by administered for diagnostic purposes, the long- patients in a simple and rapid way. lived parent or other radionuclidic impurities THEORETICAL CONSIDERATIONS will, if present, add to the radiation dose incurred by patients. T h e absorbed dose due to radiopharmaT h e nuclear reactions used to produce a ceuticals prepared using generator produced radionuclide influence the radionuclidic purity radionuclides depends on the activity of the of the nuclide. Thus, fission product and principal radionuclide and the summation of THE INCREASINGuse of short-lived radionuclides,

:-~

667

668

L. G. Colorabetti

activities due to radionuclidic contaminants at the time of the administration to the patients. The radiation dose absorbed by the patient is usually calculated on the basis of the radioassay data for the eluates from the generators which are normalized to the time of eluation. Thus the patient dose will depend also on the time lag between milking and administration to the patient. Let us call A~o and A,o, respectively, the activity of the principal radionuclide in the eluate and that of one of the radionucUdic contaminants at eluation time. The ratio fo = Aoo/A~o expresses the fraction of the contaminant activity in relation to the activity of the principal radionuclide at the time of eluation. After a time interval At from the elution time to the time of administration to the patient the ratio of contaminant activity to principal activity is: An At Aooe-a°~t Aoo A, zxt = ~ = ~ eta'-x" at, (1)

If the hag-life of an impurity is much greater than that of the principal radionuclide, which is true in most significant cases, equation (3) can be simplified: /3 = D,(1 + df.,~. ~) (5) Making this assumption let us consider the fraction of the absorbed dose due to only one contaminant, and relative to that of the principal radionuclide: F°

Do -

-

D~ -- dr°ca'in = df°e(O'n93/T)A'

(6)

The relative dose equivalent, d, can be determined using the equation for the dose absorbed by a target volume, v, from activity present in a source region, r: D = "g" ~ A , ~ .

(7)

where -~r is the accumulated activity in region r, m, is the mass of volume v, Ai is the equilibrium dose constant and ~b~ is the absorbed fraction of energy for the/-type radiation. Then, for the relative dose equivalent,

where g~ and go are the decay constants of the principal and contaminant radionuclides, respectively. Considering dn and do the dose equivalents due to a unit of activity of the principal radionuclide and contaminant radionuclide, respectively, the ratio d = d,[d~, represents the relative dose equivalent of the contaminant in relation to that of the principal radionuclide. where the accumulated activities are calculated The total dose to the body or organ of on the basis of unit activity administered. When interest is given by: the uptake of the radioactive pharmaceutical is instantaneous and the radiopharmaceutical is D(rad) = D , + D0, excreted at a monoexponential rate with half where D~ and D 0 are the total dose absorbed by time Tb, then the accumulated activity: the body or organ of interest due to the principal ~ , = 14.4AoTon , (9) and contaminant radionuclides respectively. where Tgi~= 7"1721+ Tb-1. Therefore, the Expanding; relative dose equivalent is given by: h = d~,A~A, + doAot~ (2) and substituting equation (1) into equation (2) we obtain: D = Dr1

+

aloe'a, -~.~ at].

Cl0

(3)

DISCUSSION The eluates from generators contain more Using equation (6), we can easily determine than one radionuclidic impurity so that the the absorbed radiation dose from each of the total radioactive dose is given by the following radionuclide impurities present in the eluates equation: to that of the principal radionuclide for z~ = O,(1 + ~, ado,~,-~o, ~%. (4) relative any radionuclide generator available/s~ t

Rapid estimation of the radiation dose to patientrfrom radionutlidic impurities in duates

669

TABL~ 1 _ It,IDIONUCLIDE 99110

PHYSICAL HALF-LIFE 67 h

ABSORBEDDOSE (mrod/uCt

ORGM

"DOSEEQUIVALENT" "d"

Total BodY Ltver

0.4 30

31 1250

1.70 1400 2.5

70 2800 170

1311

8.08 d

Total BOCy Thyroid Gonads

134Cs

2.05 y

Total Body Liver Gonads

46 110 62

3520 2200 4130

lO3Ru

39.5 d

Total Body Kidneys

11 130

845 1300

Total Body

585

45000

106Ru (106Rh) 60Co 86Rb

132I

369 d 5.25 y 18.7 d

2.3 h

Total Body

3.5

ToLal Body Liver

10 21

Total Body Thyroid

1.0 15

270 770

420 77 30

nOmA0

255 d

Total Body Liver

5 11

385 220

95Nb

35 d

Total Body Liver

18 34

1390 680

9SZr

65.B d

Total Body

64

490

99mTc

6.06 h

Total Body Thyrotd Lt vet Ktdne~s Gonads

Normalizing to unity the absorbed dose due to the a 'Tc, the principal radionuclide in eluates from the aMo-99'nTc generators, we calculated the dose equivalent, d, for some contaminants present in a"Tc obtained b y different procedures of extraction. (9) T o calculate the absorbed radiation dose from the principal radionuclide and impurities the MIR.D (t°) procedures were followed. T h e relative dose equivalents, d, for each radionuclide contaminant studied are summarized in Table 1. T h e computations considering ag"Tc, a~Mo

0.013 O.5 O.OS O.l O.015

1 1 1

1 1

and xalI take into account data on the biological behavior of these radionuclides, which were critically reviewed by C~nc.A and Vp.sET.Y.(?) T h e values of the absorbed dose due to a°~Tc are in agreement with those obtained by these authors and lie in the range given b y Hnca and JOHNSTOn.m) aaMo was assumed to be present in the eluate as molybdate which is excreted with a biological half-life of 20 days, and it was also assumed that 75 ~ of the aMo was taken up by the liver. T h e absorbed dose due to lsaI, which was assumed to be present as iodide, was calculated

670

L. G. Colombetti

assuming that the thyroid gland was not blocked and that uptake was 40 ~o- T h e effective halflife of t81I for the thyroid and total body was considered to be 7 days. No reliable information was found on the in vivo chemical form and kinetics of retention of a°SRu and l°6Ru. The experimental data from the literature cannot serve as a suitable guide for the dose calculations because of the considerable range of the retention and distribution values reported. Therefore, it seems reasonable to base the calculations on the assumption that these radionuclides are not excreted. T h e actual values for the radiation dose absorbed m a y be considerably lower as suggested by the experimental data reported by STAm~tt~ on the metabolism of the radionuclides in various chemical forms. T h e fraction of the impurity activity, fo, contained in the total activity of the eluate can be easily estimated by applying the findings from the g a m m a spectrometric assays. Finally the factor exp (0-693 A t / T ) can be calculated from the published half-fives and the time between elution and administration of the radioactivity to the patient. T h e practical use of equation (6) is illustrated by the following example. Suppose that at milking time the eluate from a 99Mo-99"Tc generator contains the following impurities, per mCi of ~'~Tc: 0"5 pCJ 99Mo 0-1 p C i t84Cs and that the patient is injected three hours after milking. For 99Mo, calculations arc m a d e substituting the values: d = 1250 for liver and 31 for total body (Table 1). exp (0.693 A t ] T ) = 1"4, and, concentrations of thc impurities are as shown above. Multiplying these three values

we obtain: F(Liver) = 1250 × 1.4 × 0.0005 = 0"87 F ( T o t a l Body) = 31 × 1.4 × 0.0005 = 0"02. Thus the 99Mo absorbed dose to the liver and total body is respectively, 87 ~o, and 2 % of that from the 99"Te. I n a similar m a n n e r we can calculate the aS~Cs absorbed dose as being 30 ~o, 50 ~o and 58 ~ of the DgmTc dose to liver, total body and gonads, respectively. Acknowledgement--I am pleased to acknowledge the assistance ofVAcLAVH u ~ m developing the mathematical formulation. REFERENCES 1. ROBINSONG. D. J. nucl. ivied. 13, 318 (1972).

2. BARRALR. C., SurrH S. I., Fms'roN R. A. and COLOMBETTIL. G. Acta Universitatis Carolinae 2, 377, (1973). 3. MEINHOLD H., I-IZRZ.eERO B., KAUL A. and ROEDLERH. D. IAEA Report SM-171130. (1973). 4. CoLomm~rt L. G., Hus~: V. and DVORAK V. Int. J. appl. Radiat. Isotopes 25, 35 (1974). 5. COLOMeZTrXL. G., BAR~AL R. C. and FINSTON R. A. Int. J. appl. Radiat. Isotopes 20p 717 (1969). 6. BXRR~ R. C., CrtAx~x~ V. M., COLOm3STrX L. G. and FINSTON R. A. Int. J. appl. Radiat. Isotopes 22, 149 (1971). 7. CxyKAJ. and VESELY P. Report UJV 2696-D, Rez (1971). 8. COLO~m'TX L. G. and H u s ~ V. Proc. Health Physics Problems of Internal Contamination S.ymp., p. 155, Budapest (1972). 9. COLOMnFTTIL. G. and B~a~Es W. E. Int. J. apt. Radiat. Isotopes 25, 455 (1974). 10, BROWNELLG. L., ELLETTW. H. and R.EDDYA. R. J. nucl. Med. Suppl. 1, 27 (1968). 11. H~E G . J . and JOt-n~STONR. E. J. nucl. Med. lip 468 (1970). 12. S T ~ J . F., NEmo~ N. S., D~LL~RoaA R. J. and BUSTARD L. Hlth. Phys. 20, 113 (1971).