Excretion of Iodine- 123-Hippuran, Technetium-99m-Red Blood Cells, and Technetium-9 9m-Macroaggregated Albumin into Breast Milk Marjorie R. Rose, Mary C. Prescott, and Kenneth J. Herman Departments ofNuclear Medicine and Medical Physics, Manchester Royal Infirmary, Manchester, United Kingdom the interruption period was always 24 hr but this varied Theamountof radioactivityexcretedin breastmilkfollow latterly as new guidelines appeared (3) and our expen ingthree differentnuclearmedicineprocedureson twelve ence grew. nursingmothershas beenmeasured.Someof this infor mationhasalreadybeenincorporatedintothe latestguide MATERIALSAND METHODS lineson suspensionof feedingafter maternalradiophar maceuticaladministration.The overallradiationdose that Patients the patients' babies would have sustained had breast Details of the radiopharmaceuticals administered to the feeding not been interrupted has been estimated as an mothers and the ages of their babies are given in Table 1. effectivedoseequivalent.A modelhas beendevelopedto Three patients underwent renography. The ‘231-hippuranad describe the relationshipbetween clearance of activity ministered to Patient H I was estimated to contain 5% free from the milk, time between expressions, and the fraction iodide, 5% iodobenzoic acid, and 0.2% 1251(Harwell, Eng of milk expressed. Some simple guidance is given on land). Frusemide (Furosemide) was administered to this pa calculationof suitableinterruptiontimesfor any individual tient 19.5 mm after the start of the test. The ‘231-hippuran motherfromcountson her milksamples. administered to Patients H2 and H3 contained <2% free J NucI Med 1990; 31:978—984 iodide and no 125!(Mallinckrodt Diagnostica). Venography was performed on three of the patients. For Patients RI and R2, the red cell labeling agent, stannous medronate (Amersham International) was administered intra venously followed by [99mTc]pertechfletate20 mm later. For ata on the excretion of radiopharmaceuticals into Patient R3, Pyrolite(NEN Du Pont, N. Billerica,MA) was breast milk following nuclear medicine procedures is used as the red cell labeling agent and the pertechnetate was administered after 5 mm. The activity administered is higher available for some of the tests commonly performed. where first-pass images were requested. However, there is only one set of published data for The remainingpatients had lung scansusing @mTc@MAA. iodine-123-hippuran (‘231-hippuran)(1); in addition, Pulmolite (NEN Du Pont) was used for Patient M6 but all results obtained following in-vivo labeling of red cells the others received MAA from the Mallinckrodt kit. All the with technetium-99m (99mTc) are scarce (2) and might patients except M3 also inhaled kryptom-8 lm ($ImKr)gas but be expected to vary between patients since the labeling this was not considered in the calculations. efficiency is known to vary. Results obtained on six nursing mothers are therefore RESULTS presented and six others who received 99mTc@macroag@ gregated albumin (MAA) have been included for com The results are summarized in Figure 1 and Table 2. panson with other published data. The twelve women This table also includes previously published data from were advised to stop feeding for a short period and they other centers for comparison (1,2,4—7).The percentage kindly consented to send us a sample of milk expressed of the dose excreted intd breast milk was calculated in at each nominal feed time over this period. Initially, two parts. This section outlines the estimation of the most significant part which is the fraction excreted over the interruption period. The next section outlines the ReceivedMay31, 1988;revisionacceptedOct.26,1989. reasoning behind the estimation of the actual percent For reprintscontact:MarjorieA. Rose, MPhII,Departmentsof Nudear MedicineandMedicalPhysics,ManchesterRoyalInfirmary,OxfordRd., age ofthe dose ingested by the child after breast feeding Manchester,UKM13 9W1. was resumed. 978 The Journalof NuclearMedicine•Vol. 31 •No. 6 •June1990 TABLEI .2 Resultsof RadiopharmaceuticalsAdministeredto NursingMothers adrnin. of expressed period .1 (hr)1231-hippuranPatientnumberActivity(MBq)AgebabyVolume(ml)Interruption Hi H2 9 7rno 4i0 24 H3108@Tc 10i8d 7rnonrn nrn24 -J 0- x 0 5 10 15 20 25 in-vivo RBC U.a .02 Ri w R2 500 3d 500 24 I- B R330324@Tc-MAA 4254d 4dnrn nrn24 -I w a- . 01 Mi w U) M2 38 i5d 640 24 0 0 M3 44 6d 75 16 U. M4 44 9d 120 20 0 z M5 68 iiwk nrn 24 0 0 @ 16nrnM683 376d 6dnm nm24 I- 0 1'o 1@ 20 25 U .2 = notmeasured. U. C DoseExcretedFraction .1 The fraction of the dose excreted into breast milk over the interruption period was estimated from the injected activity and the measured concentration of activity in each expression, assuming a total volume 0 excreted over 24 hr of 850 ml (8). Almost all of the 0 10 1! babies involved in this study were either so young that HOURS AFTER INJECTION breast feeding had not been properly established or FIGURE1 Fractionof administeredactivityper literof breastmilkas a much older so that weaning had begun. It is not sur function of time after administrationof 1@l-hippuran(A), in prising, therefore, that, where complete milk collections vivolabelingoferythrocyteswith @“Tc(B),andadministration were obtained, the volume was always less than this of @‘Tc-MAA(C). figure. Table 1 gives the individual values. However, since there are good reasons to doubt that the volume of milk expressed would be as much as would have exponential fit of the data. We have used a different been ingested naturally (8), it was felt that no reasonable method but our estimate for Patient Hl is within the approximation could be made and the larger volume published range for ‘25I-hippuranand ‘31I-hippuran(2). should be used in the calculations. This volume was After changing the supplier, the percentage excreted assumed to be spread equally over the expressions since was reduced and is consistent with the only other set of milk was expressed as typical feed times. Hence: published data for ‘23I-hippuran,which was obtained from the same source (1). This confirms the warnings ‘1' often given in the literature that the fraction of activity F1= {@r@i(c@x 850/n x t/24)}/ D, ‘. I excreted in breast milk after administration of hippuran is critically dependent on chemical purity which varies where F1is the fraction of the dose excreted in breast from supplier to supplier and at different times from milk over the interruption period of t hr, C@is the the same supplier as the radiopharmaceutical is im concentration of activity in MBujml from the ith proved. expression, and D is the injected activity in MBq. This The percentage excreted after 99mTc..redblood cells is fraction is expressed as a percentage in Table 2. The around two ordersofmagnitude higherthan that found number of expressions, n, varied between 3 and 6 for by Ahlgren (2). This suggests that we obtained a poorer those patients studied over 24 hr. labeling efficiency than Ahigren did in his patient. The percentage of the dose excreted in breast milk is For 99mTc@MAA,our resultsare within the published most often reported as an estimate to infinity from an range which is wide. Excretionof RadioactivityinBreastMilk •Roseat al 979 TABLE 2 Dose ExcretionResults (baby) no. dose rnSv/MBq motherfHippuran123lHi5.i3.50.i20.3i1231H25.02.00.060.23123,H35.7iRadionuclidePatient or ref.eff.% excretedHE to .20.040.201231ref. @ i3.5i .2 0.581251ref. i .7t0.05 0.07— 24.82.4——1311ref. 22.2—5.8i.8—4.9——@“Tc-red blood cellsRi R2 7.2 i.0 0.0034 R3 9.5 0.2 0.00056 0.00002@“Tc-MAAMi ref. 26.8 7.70.6 0.0060.00i9 M2 4.i 5.4 0.0i9 0.25 M3 3.6 3.7 0.0i2 0.28 M4 2.6 0.5 0.00i8 0.55 MS 5.4 0.4 0.0015 — M6 4.4 2.0 0.0068 0.i9 ref. 2 3.3—4.5 0.4—5.2 0.OOi—0.0i8 — ref. 4 2.8 0.5 0.002 0.68 ref. 5* 4.6 3.3 0.0i2 0.3i ref. 6 3.4—4.8 0.2—2.8 0.OOi—0.0i0 0.37 —. ref. 7‘@@4.7 —5.4 0.40.019 0.0020.3i reported.tAs onginially method.*Calculated by our Includes a contribution from @“Tc-DTPAaerosol. For all radiopharmaceuticals, the effective half-life nuclides. However, the corresponding biologic half-lives calculated from our results was in reasonable agreement are 2.2—6.0hr for ‘311-hippuranand 4.8 hr for 1251.. with any previously published data. This aspect of the hippuran. Certainly the results of Mountford et al. are work is also considered in more detail in the next more consistent than our own since these workers ob section. tamed a biologic half-life of 4.8 hr with 1231-hippuran (1). DISCUSSION This discrepancy could be due to variations in the biologic distribution of tracer between patients. How TheExpressedMilkModel ever, we have developed a model which offers a more We have noted the wide range of effective secretion plausible explanation and it is based on consideration half-lives obtained by ourselves and others. In particu ofthe nature ofthe ‘biologic'decay for this type of data. lar, we were intrigued by the results we obtained after It seems to us that the decrease in the activity of the administration of ‘231-hippuran.In all three cases, these milk over and above the physical decay will be almost were similar to those reported for ‘251-hippuranand ‘@‘ientirely due to the previous expressions of milk. Re hippuran (2). Ifwe use the well-known relationship: sorption of label from the milk back into the mother's T@ff Tb T@/(T@+ Tb), (2) @@odyis likely to be insignificant by comparison.