Intercomparison of 131 I and 99m Tc Activity Measurements in Brazilian Nuclear Medicine Services

Intercomparison of 131 I and 99m Tc Activity Measurements in Brazilian Nuclear Medicine Services A. Iwahara 1, A. E. de Oliveira 1, L. Tauhata 1, C. J. da Silva 1 and R. T. Lopes 2 1 Laboratório Nacional de Metrologia das Radiações Ionizantes-Instituto de Radioproteção e Dosimetria- Comissão Nacional de Energia Nuclear/Av. Salvador Allende, s/n, Recreio Rio de Janeiro Brazil - CEP 22780 160 2 Laboratório de Instrumentação Nuclear-Coordenação dos Programas de Pós-Graduação de Engenharia- Universidade Federal do Rio de Janeiro PO Box 68509 Rio de Janeiro Brazil - CEP 21945 970 INTRODUCTION Radioactive materials have been widely used in medical practices for purpose of diagnosis and therapy. There are, in Brazil, 247 Nuclear Medicine Services (NMS) and concentrated mainly in the South-East region (152 Services - 62 %) where the most developed Brazilian states are localized. The determination of the activity to be administered to the patient plays an important role on the quality of the clinical result of a medical investigation. Thus, the activity should be correctly quantified and the most suitable instrument is the activity meter (formerly called dose calibrator). There are many references in the literature where protocols and quality control procedures for such a instrument are recommended (1-5). In spite of a good quality control program, the activity meter can produce incorrect measurements due to a number of reasons: a) variation in response among different containers (this is particularly critical for low photons energy emitter); b) radioactivity impurities resulting in the overestimation of the activity; c) physical surrounding of the activity meter (an additional shielding can increase the radiation back-scattering invalidating the calibration of the instrument for high energy gamma emitters) and d) samples improperly placed in counting supports. In order to investigate the performance on the quality of routine measurements carried out in the NMS, an pilot program of intercomparison was organized between the National Laboratory for Ionizing Radiation Metrology (LNMRI) and medical community. LNMRI is the Brazilian National Laboratory in the field of ionizing radiation and has the mission to maintain, disseminate and establish traceability of radioactivity standards and measurements to the whole country. In this pilot program only those NMS placed in the Rio de Janeiro city have participated. After consultation and concern demonstrated by the medical community the nuclides 131 I and 99m Tc were chosen for this intercomparison. Participation was voluntary and included public and private hospitals. This intercomparison program seeks to obtain the information on the quality of routine measurements carried out in the NMS using activity meters, the analysis of possible contaminants in the samples, the evaluation of the uncertainties and the exchange of information. Other specific aim is to identify areas in which radionuclide metrologists can give support to medical user of radionuclides. METHODOLOGY The methodology of the intercomparison can be divided in two stages: 1) at NMS: a) preparation of the activity sample to be administered to the patient, as routinely; by the operator responsible; b) measurement of the background of the activity meter; c) measurement of the sample three times. This will allow the error due to the slight changes in the position of the sample inside the well of the activity meter; d) write down in a data sheet, the date and time of each measure and respective result, and the model and manufacturer of the activity meter; e) measurement of the background after the last sample measurement; f) the sample is involved by a thin plastic bag, placed in a lead shield and removed to LNMRI; 2) at LNMRI: a) the sample is measured, as received, in a CENTRONIC IG12 well type ionization chamber previously calibrated using solutions which had been standardized using systems and techniques available at LNMRI; b) the plastic bag is measured in a germanium detector in order to verify any external contamination on the vial; 1

c) the sample is measured in a germanium detector in order to assay the radionuclidic purity. In the case of 99mTc, the possible presence of 99Mo will be checked. d) the result of ionization chamber measurement is adopted as the reference value for the intercomparison. INTERCOMPARISON All samples of the intercomparison were contained in a 20 ml serum vial and most of them with 5 ml of the solution. Those of less than 5 ml were completed with distillated water to this volume before the measurement in the ionization chamber. Each participant received a code number without associating the name which performed the measurements. In order to compare the results, the activities measured an LNMRI were decayed to the measurement times as stated by the participants. The half-lives adopted were 8.021 ± 0.001 and 6.007 ± 0.012 days for 131 I and 99m Tc, respectively. The analysis of the contamination studies has demonstrated absence of any contaminant in the case of 131 I. The presence of the 99 Mo in the 99m Tc samples has ranged within the limits prescribed by United States Pharmacopoeia (USP) whose amount of 99 Mo should be less than 5.55 kbq (0.15 µci) per 37 MBq (1 mci) of 99m Tc at the time if administration. Most of the plastic bags that involved the samples were contaminated. The level of these contaminations were estimated ranging from 3.7 to 37 kbq. As the activities of the samples were greater than 1.0 MBq for 131 I and 50 MBq for 99m Tc, these contaminations would yield an error, at most, of 3.7 % for 131 I and 0.07 % for 99m Tc measurements at NMS. The majority of the NMS have demonstrated difficulties or even in stating the uncertainties on their measurements. In this intercomparison, the type A uncertainty (random) of the NMS results was the standard deviation of the three measurements. The type B (non-random) was adopted as the deviation of the mean of the three measurements from the reference value determined by the ionization chamber at LNMRI. The overall uncertainty was determined quadratically in the usual way. ANALYSIS OF THE PERFORMANCE The participants results were compared with the LNMRI results in two ways. First, by calculating the simple relative deviation of the participants results from the LNMRI results. This simple approach permit verify if the participants measurements comply with the accuracy recommended in the norm of Brazilian Regulatory Authority which permit an upper limit of ± 10 %. Second, the statistical criteria called normalized standard deviation, D, were used for the analysis of the performance of the measurements (6, 7). D is defined as the difference between the NMS mean value of three measurements, X, and the LNMRI reference value, U, normalized to the standard deviation of the reference value, S U, divided by measurements (n = 3 for this intercomparison). D is calculated as 3, where n is the number of D = X U S U 3 The parameter D can be used to classify the participants performance in good, acceptable and nonacceptable according to the specified limits (Table 1). 2

Table 1. Normalized standard deviation Normalized Standard Deviation D Performance -2 D +2-3 < D < -2 or +2 < D < +3-3 D +3 good (within all limits) acceptable (within the warning limits) non acceptable (out of control limits) For the purpose of this intercomparison program, we have adopted S U = 0.05U by conservative reasons because the Brazilian norm for activity measurements at Nuclear Medicine Services requires an upper limit of ± 10 % of deviation from U. This adopted value is much larger than the uncertainty of the U obtained at LNMRI, which is less than 1 %, both for 131 I and 99m Tc. If the uncertainty obtained at LNMRI was adopted, most of the results determined by the NMS would be considered not-acceptable. The results and the performance of the intercomparison are presented in Table 2a and 2b, and Figures 1a, 1b, 2a and 2b. DISCUSSION The results displayed in Figure 1a for 131 I shows that 65 % complies with the upper limit of ± 10 % recommended by the norm of Brazilian Regulatory Authority for the accuracy of the measurements aimed at. In individual cases, however, deviation of the order of 41 % can be observed. For 99m Tc, however, 85 % of the results are within the limit of ± 10 % accuracy (Figure 1b). This seems that measurements performed routinely for 99m Tc in the NMS were better than for 131 I no matter the type of the activity meter. One possible contribution for this is the range of activities that were much larger for 99m Tc than 131 I. This effect will be investigated. In this present intercomparison,it was observed that those Services that make quality control tests of activity meters don t check linearity performance. The mean values for R, calculated from Tables 2a and 2b are 1.06 ± 0.18 (17 %) and 0.98 ± 0.08 (8 %), respectively for 131 I and 99m Tc. From these values, it can be noticed a tendency of an overestimation of activity values for 131 I and an underestimation for 99m Tc. In terms of performance D, 50 % of the results were good, 10 % acceptable and 40 % were out of control for 131 I (Figure 2a). For 99m Tc, 53 % were good, 27 % acceptable and 20 % were out of control (Figure 2b). 3

1. Table 2a. Results and performance of 131 I intercomparison. Participant Code Activity Meter NMS Activity Concentration (MBq g -1 ) Value Uncertainty* (k = 1) LNMRI Activity Concentration (MBq g -1 ) Value Uncertainty* (k = 1) NMS/LNMRI Activity Concentration Ratio (R) Performance D GB1 1.038 0.068 0.984 0.049 1.05 1.90 GB2 0.966 0.111 0.984 0.049 0.98-0.64 CD CAPINTEC 10BC 0.218 0.004 0.215 0.011 1.01 0.47 LM 3.555 0.478 3.581 0.178 0.99-0.25 ST 12.133 0.029 12.104 0.605 1.00 0.08 EJ 1.569 0.690 1.110 0.056 1.41 14.20 XK 1.484 0.435 1.082 0.054 1.37 12.89 AJ 0.655 0.106 0.569 0.028 1.15 5.32 IB CAPINTEC 10- PC 0.501 0.022 0.479 0.024 1.04 1.59 HA1 0.673 0.209 0.569 0.028 1.18 6.43 HA2 CAPINTEC 7 0.613 0.047 0.569 0.028 1.08 2.54 MR ATOMLAB 200 1.250 0.074 1.324 0.066 0.94-1.94 PG CAPINTEC 127R 1.730 0.414 1.313 0.066 1.32 10.94 DB CAPINTEC 12 3.463 0.225 3.256 0.163 1.06 2.20 PT 4.773 0.504 4.608 0.230 1.04 1.22 LK1 4.155 0.881 3.434 0.172 1.21 7.26 LK2 CAPINTEC 5R 3.308 0.549 3.413 0.171 0.97-1.06 LT 4.932 0.661 5.495 0.275 0.90-3.55 BC 3.212 1.323 5.450 0.273 0.59-14.20 JU 3.648 0.099 3.748 0.187 0.97-0.93 *Coverage factor for 68.27 % level of coincidence 4

Table 2b. Results and performance of 99m Tc intercomparison. Participant Code Activity Meter NMS Activity Concentration (MBq g -1 ) Value Uncertainty* (k = 1) LNMRI Activity Concentration (MBq g -1 ) Value Uncertainty* (k = 1) NMS/LNMRI Activity Concentration Ratio (R) Performance D DB CAPINTEC 12 9.97 1.12 8.96 0.45 1.11 3.92 PT 285.6 10.50 276.1 13.80 1.03 1.19 CD CAPINTEC 10BC 72.79 3.45 76.42 3.82 0.98-1.64 LK1 73.47 3.08 70.65 3.53 1.04 1.39 LK2 CAPINTEC 5R 65.67 5.31 71.44 3.57 0.92-2.80 DF 89.47 6.15 83.74 4.19 1.07 2.37 BC 69.50 5.14 75.04 3.75 0.93-2.56 LT 106.00 7.28 101.11 5.06 1.05 1.68 JU 715.25 46.71 765.20 38.26 0.93-2.26 LM CAPINTEC CRC-5 225.18 9.37 234.96 11.75 0.96-1.44 MR ATOMLAB 200 162.80 32.49 203.40 10.17 0.80-6.91 GB1 214.45 7.51 221.36 11.07 0.97-1.08 GB2 CAL/RAD 211.94 11.28 222.64 11.13 0.95-1.67 IB1 RAD/CAL II 104.34 3.90 101.97 5.10 1.02 0.81 IB2 CAPINTEC 93.24 9.48 CRC-10PC *Coverage factor for 68.27 % level of confidence. 102.56 5.13 0.91-3.15 5

2,50 NMS/LNMRI Activity Concentration Ratio 2,00 1,50 1,00 0,50 0,00 GB1GB2 CD LM ST EJ XK AJ Nuclear Medicine Services (NMS) IB HA1HA2 MR PG DB PT LK1 LK2 LT BC JU Figure 1a. NMS/LNMRI activity concentraton ratio for 131 I intercomparison. NMS/LNMRI Activity Concentration Ratio 1,30 1,20 1,10 1,00 0,90 0,80 0,70 0,60 DB PT CD LK1 LK2 DF BC LT JU LM MR GB1 GB2 IB1 IB2 Nuclear Medicine Services (NMS) Figure 1b. NMS/LNMRI Activity concentration ratio for 99m Tc intercomparison. 6

35 30 Out of control >3 Relative Frequency (%) 25 20 15 10 <-3 Good performance Acceptable 5 0-3 -2-1 0 1 2 3 Normalized Standard Deviation (D) Figure 2a. Performance of the NMS measurements for 131 I intercomparison. 30 Out of control Relative Frequency (%) 25 20 15 10 <-3 Good performance Acceptable >3 5 0-3 -2-1 0 1 2 3 Normalized Standard Deviation (D) Figure 2b. Performance of the NMS measurements for 99m Tc intercomparison. 7

CONCLUSIONS This intercomparison comprised only the Nuclear Medicine Services placed at Rio de Janeiro city. The total of NMS in the city is 25, so that the number of participants (17) corresponds to 68 %, for 131 I, and 48 % (12 participants) for 99m Tc. This means that further effort should be done to increase the number of participants in the future intercomparison runs. For those NMS whose results are beyond the upper limits of ± 10 %, a recalibration of the instrument was recommended and invited to participate to a new intercomparison run. On the other hand, if more stiff statistical criteria like parameter D to evaluate the performance of the measurements was adopted, a great effort should be carried out to bring the results considered out of control into the acceptable limits. Those Services that routinely make quality control tests with checking sources have produced better performances. The participation is not mandatory but due to the concern of the public about the use of the radiation in general, more and more NMS have demonstrated interest in participating to the future intercomparison runs. Other consideration is about the uncertainties where the majority of the participants demonstrated difficulties to state them. This will be discussed in a near follow up meeting with the LNMRI and the participants. REFERENCES 1. American National Standards, Calibration and usage of dose calibrator ionization chambers for the assay of radionuclides. ANSI N42.13 (1986). 2. M.J.Woods, W.J.Callow and P.Christmas, The NPL Radionuclide Calibrator-Type 271. Int. J. Nucl. Med. Biol. Vol. 10, No. 2/3, 127-132 (1983). 3. Suzuki, M.N.Suzuki and A.M.Weis, Analysis of a Radioisotope Calibrator. J. Nucl. Med. Tech. Vol. 40, No.4, 193-198 (1988). 4. Aubert, M.Despres, J. Gory, A.Lisbona and M.Ricard, Étallonage et Contrôle des Activimètres. Rapport S.F.P.H. No. 10 (1995). 5. A Parkin, J.P.Sephton, E.G.A.Aird, J.Hannan, A.E.Simpson and M.J.Woods, Protocol for Establishing and Maintaining the Calibrationof Medical Radionuclide Calibrators and their Quality Control. Institute for Phyhsical Sciences in Medicine, Report No. 65, 60 (1992). 6. M.G.Natrella, Experimental Statistics. NBS Handbook No. 91, 3-8 (1963). 7. N.A.Jarvis and L.Siu, Environmental Radioactivity Laboratory Intercomparison Studies Program. U. S. EPA-600/4-81-004 (1981) 8