Eur J Nucl Med (1985) 10:60-62 European M I I~I~,'~r Journal of I ~IUI~./ I~(: : ; I , /

Medicine © Springer-Verlag 1985

Bromine-82 contamination in fission product 99mTc-Generator Eluate Robert MeAuley 1, Robert Lull 2, and Rodney Ice 3 1 College of Pharmacy, University of Oklahoma, USA 2 Nuclear Medicine Service, Letterman Army Medical Center Presidio of San Francisco, California, USA 3 Benedict Nuclear Pharmaceuticals Inc., Golden, Colorado, USA

Abstract. Following receipt of fission product 99mTc-gener- ators, results of radionuclide purity analysis, performed within 30 min after the first elution, demonstrated detect- able levels of a contaminate radionuclide not previously reported. Gamma spectroscopy and half-life determinations confirmed the presence of S2Br. Bromine-82 activity, in 322.2 6,245 - eluates from the first elution of 30 generators, received 497.0 2,985 100.0

554.3 3,510 70.7 weekly during a 7-month period, ranged from 0.22 gCi 618.9 2,168 43.0 (8.235 kBq) to 0.67 pCi (24.68 kBq) per eluate. The ratio 698.2 1,508 28.6 of 99M0 to 99mTc ranged from 0.13 nCi to 0.39 nCi per 739.3 2,841 12.6 mCi 99mTc. The presence of 82Br in 99mTc-generator ehiate 776.5 5,206 - resulted in falsely elevated 99Mo assay determinations using 776.49 4,214" 83.4 whole vial 99Mo assay procedures. For every 0.1 gCi 82Br 777.8 992" 4.4 present in 99mTC eluate the 99Mo assay results were elevated 827.7 1,241 24.2 by 1 gCi. Gamma spectroscopy of eluates from additional 1,043.8 1,157 27.4

1,317.4 1,042 26.8 elutions of these generators failed to detect the presence of SZBr demonstrating the displacement of monovalent bro- mine anions from the alumina column during the first elu- tion.

The importance of identifying and determining the signifi- cance of radionuclide impurities associated with fission product 99M0 is well established Anderson etal. 1974; Briner and Harris 1974; Vinberg and Kristensen 1976; and others).

As part of our nuclear pharmacy quality control pro- gram, eluates from fission product 99mTc-generators under- went routine gamma spectroscopy to determine radionu- clide purity and to quantitate the activity of 99Mo break- through. During routine pulse height analysis of energy spectra we consistently observed six incidental peaks (554.3 keV, 618.9 keV, 698.2 keV, 827.7 keV, 1,043.8 keV, 1,317.4 keV) unassociated with radionuclides previously reported as possible contaminates of fission product 99mTc-genera- tors (Vlcek et al. 1979; Nasman and Vayryman 1983). Re-

The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Army or the Department of Defense.

Offprint requests to: LTC Robert J. McAuley, MS, College of Pharmacy, University of Oklahoma, 1110 N. Stonewall Oklahoma City, OK 73190, USA

Table 1.99mTg eluate gamma spectrum results

Energy cpl0m % Radio- T(1/2) keV Abundance nuclide

99mTc lO3Ru S2Br 82Br SZBr 99Mo 99Mo/SZBr 82Br 99Mo 82Br S2Br 82Br

6.0h 39.6 d 35.3 h

66.02 h

a Calculated

cently (Jedlovszky and Szorenyl 1983) reported 82Br impu- rity associated with 99mTc but did not suggest the method of 99mTC production.

Each of the unidentified energies corresponded to ener- gies characteristic for 82Br as shown in Table 1. The prima- ry 776.45 keV gamma (83.4% abundance) for S2Br overlaps the 777.6 keV gamma (4.4% abundance) for 99Mo (Lederer and Shirley 1978). Bromine-82 is not a fission product and therefore would not be expected to be a possible radioconta- minate of fission product 99mTc-generators.

This study was initiated to address the following specific considerations: (a) the source of 82Br contamination and its frequency of occurrence; (b) significance related to pa- tient safety; (c) effect on 99M0 breakthrough determina- tion; and (d) methods to reduce or eliminate 82Br contami- nation.

Materials and methods

Eluates from 30 fission product 2.222-Ci (82.214 GBq) 99mTc-generators (Squibb), received weekly, underwent routine gamma spectroscopy within 30 min postelution. En- ergy spectra from 3.7 keV to 1.38 MeV were recorded with a high-resolution Ge(Li) detector coupled to a 2,048-multi-

61

channel analyzer (MCA). The F W H M ranged from 2.4 to 3 keV over the entire spectrum.

All standards and samples were counted with the same vial shielding, constant geometry, and the results corrected for background.

Instrument calibration was performed with 5 VCo ' 137Cs ' and 6°Co standards traceable to the National Bureau of Standards (NBS). Detector efficiencies of 0.05184% and 0.05137% for the 739 and 777 keV energies were determined with a shielded NBS 99Mo standard. The activity of S=Br was calculated by:

Ab_ l - - (M) (R) (E) (D) (P)

were Ao=82Br activity; / = n e t integrated counts in peak 777 keV; M = n e t integrated counts in peak 739 keV; R = 0.349 (777 keV/739 keV gamma ratio for 99Mo); E = 0.05137 (% detector efficiency at 777 keV); D=3.7 x 104 dps/gCi; P = 83.4 (% abundance for 82Br 777 gamma). The significance of 82Br contaminate to falsely elevate 99Mo assay results, was determined by MCA spectral analysis 0.6-1.0 MeV using 99Mo/S2Br mixtures with known activi- ties. Half-life determinations were performed on individual energy spectra to confirm the presence of 82Br.

R e s u l t s

Analysis of gamma spectra from the first elution of fission product 99mTc-generator eluates, from 22 November 1980 to 31 August 1981, consistently demonstrated energy peaks characteristic for S2Br as shown in Fig. 1. The mean half-life for each of the peak energies identified as characteristic for S2Br was 34.0 (_+0.5) h. The activity of 82Br ranged from 0.22 gCi (8.235 kBq) to 0.67 gCi (24.684 kBq) per elution. The ratio of S2Br to 99mTc ranged from 0.13 nCi to 0.39 nCi per mCi. The activity of S2Br, by itself, was several orders of magnitude below the United States Phar- macopeia (USP) limit of 0.1 gCi/mCi 99mTc specified for all other beta gamma emitters.

TIME (L)= 600 15:55 22 NOV 80 PSET (L)= 600 Unit # 1 DT= 2%

3~7 KEV VFS= 4096 CRT= (01-08) 1381.4 KEV

x

eq

5¢ ¢o o ~ >~

5¢ > c q b -

.: . ~ ~ . > ~ >

i " ~ ~ ~ >

i

_ i • [

LC= &7 KEV INT = 483503 CPS = 805.8 RC=1381.4KEV 600 CP10M 2 CP10M

Fig. 1. Gamma spectrum of 99mTC eluate from 22 November/980 demonstrating characteristic peaks for S=Br

The radiation absorbed dose contribution from ~2Br, following administration of 20 mCi (0.74 GBq) 99mTc, 6 h after assay, would result, at the most, in a dose of 0.02 mrad to the total body using MIRD estimates (Snyder et al. 1975). Therefore a2Br is not expected to adversely effect patient radiation safety but its contribution must be consid- ered when determining the total activity from all other beta gamma radiocontaminates.

After the first elution, additional column washings (elu- tions) failed to produce eluate with detectable amounts of S2Br. The apparent low affinity of S/Br for alumina suggests that SZBr is present as the monovalent bromine anion and is displaced from the alumina column with 0.9% NaC1 (Steigman 1982).

Radionuclide analysis of fission product 99Mo con- firmed the presence of 82Br. Fission product 99Mo is pro- duced by 'irradiating 235U with thermal or fast neutrons in a nuclear reactor ' (Molinski 1982). The molybdenum- 99 is separated from other fission products by one of a number of techniques. Of the fission products, about 0.2% is stable bromine-81 which undergoes neutron activation (SlBr(n, 7)82Br) to form SZBr. Theoretical calculations in the amount of S2Br produced by this reaction, correlates with the contamination levels found in fission product mo- lybdenum-99.

The presence of S2Br contamination, resulted in falsely elevated 99Mo assays. 99Mo assay results were increased 1 I~Ci for every 0.1 gCi of aZBr contaminate. The upper level of 82Br contaminate (0.67 I~Ci) found in the 99mTc eluates studied, falsely elevated the whole vial 99Mo assay by 7 tlCi. Radionuclide analysis of first elutions from three other generator manufacturers (Cintichem, Mallinckrodt, NEN) failed to demonstrate similar levels of S2Br contami- nate.

D i s c u s s i o n

Our observations and those of other investigators suggest the importance of performing routine radionuclide quality control by the user. The presence of S2Br, a nonfission product, has been detected as a possible contaminate of fission product 99mTc-generator eluates. The greater photon abundance characteristic for SZBr and overlapping gamma spectra result in falsely elevated 99M0 determinations, if the shielded whole vial assay technique is employed with a dose calibrator. Prior to shipment, manufacturers routine- ly wash generator columns which should remove SZBr and other soluble radiocontaminates. Insufficient wash volume may account for the elevated levels of S2Br contaminate consistently observed during our study. The occurrence of S2Br contaminate in fission product 99mTc-generators does not appear to be universal and the extent and frequency requires further study.

R e f e r e n c e s

Anderson DW, Raeside DE, Ficken VJ (1974) Determination of impurity activities in fission-product generator eluate. J Nucl Med 15 : 889-891

Briner WH, Harris CC (1974) Radionuclide contamination of eluates from fission-product molybdenum-technetium genera- tors. J Nucl Med 15:466M67

62

Jedlovszky R, Szorenyl A (1983) Detection of radionuclide impuri- ties. Int J Nucl Med Biol 10:65-68

Lederer CM, Shirley VS (1978) Table of Isotopes, 7th ed., New York, Wiley

Molinski VJ (1982) A review of 99mTC generator technology. Int J Appl Radiat Isot 33 : 811-819

Nasman P, Vayrynen T (1983) Impurities of 99mTc-generators. Eur J Nucl Med 8:26-29

Snyder WS, Ford MR, Warner GG (1975) Estimates of absorbed dose per unit cumulated activity for selected radionuclides and organs. MIRD Pamphlet 11. New York, Society of Nuclear Medicine

Steigman J (1982) Chemistry of the alumina column. Int J Appl Radiat Isot 33 : 829-834

The United States Pharmacopeia (1980) 20th revision, Easton, Pa, Mack Publishing Co. p 765

Vinberg V, Kristensen K (1976) Comparative evaluation of 99mTc- generators. Eur J Nucl Med 1:219-233

Vlcek J, Husak V, Rohacek J (1979) Results of regular study on radionuclidic purity of 99mTc obtained from 99Mo-99myc gener- ators. Eur J Nucl Med 4:385-387

Received February 11, 1984