|Year : 2018 | Volume
| Issue : 1 | Page : 1-5
Radiation dose to the occupational worker during the synthesis of 188Re-labeled radiopharmaceuticals in the nuclear medicine department
Parul Thakral1, Jyotsna1, Pankaj Tandon2, Sugandha Dureja1, Vineet Pant1, Ishita Sen1
1 Department of Nuclear Medicine, Fortis Memorial Research Institute, Gurgaon, Haryana, India
2 Medical Applications Section, Radiological Safety Division, Atomic Energy Regulatory Board, Government of India, Niyamak Bhavan-B, Anushakti Nagar, Mumbai, Maharashtra., India
|Date of Web Publication||16-Jan-2018|
Dr. Ishita Sen
Department of Nuclear Medicine, Fortis Memorial Research Institute, Gurgaon, Haryana
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Aim: The aim of this study is to estimate whole-body radiation dose to the radiopharmacist involved in labeling of three different 188Re-labeled compounds, namely, 188Re-Lipiodol, 188Re-tin colloid, and 188Re-hydroxyl-ethylidene-diphosphonate (HEDP) and to compare the occupational burden with the dose limits recommended by Atomic Energy Regulatory Board, India. Materials and Methods: The Department of Nuclear Medicine at Fortis Memorial Research Institute currently synthesizes three different Rhenium-188 labeled compounds, namely, 188Re-Lipiodol, 188Re-HEDP, and 188Re-tin colloid. To estimate the radiation exposure to the radiopharmacist involved in the synthesis, a survey meter was used to measure radiation level before the start of labeling procedure in the radiopharmacy by keeping it at the location where the radiopharmacist normally stands during preparation. Data were collected for 6 syntheses of each 188Re-Lipiodol, 4 for 188Re-HEDP, and 3 for 188Re-tin colloid followed by the quality control. The pocket dosimeter was used by the radiopharmacistat chest level, performing the labeling of 188Re-labeled compounds. All radiopharmaceuticals were synthesized by a single radiopharmacist. Results: 1850 MBq (50 mCi) 188W-188Re generator was eluted before the preparation of each radiopharmaceutical. The amount of 188ReO4- used for labeling with lipiodol/4-hexadecyl-1,2,9,9-tetramethyl-4,7-diaza-1,10-decanethiol, HEDP, and Tin colloid was in the range of 3182–4440 MBq (86–120 mCi), 2812–3774 MBq (76–102 mCi), and 962–1295 MBq (26–35 mCi), respectively. Meantime required to complete the synthesis was 95, 40, and 131.5 min, respectively. Mean whole-body effective dose received was 0.052, 0.009, and 0.004 mSv, respectively, as measured by using the pocket dosimeter. Conclusion: From this small study, we observed that the whole-body radiation dose to the radiopharmacist in radiolabeling and quality control of 188Re-labeled radiopharmaceuticals is within prescribed limits at the current synthesis frequency.
Keywords: Radiation dose, radiopharmacy, Re-188
|How to cite this article:|
Thakral P, Jyotsna, Tandon P, Dureja S, Pant V, Sen I. Radiation dose to the occupational worker during the synthesis of 188Re-labeled radiopharmaceuticals in the nuclear medicine department. Indian J Nucl Med 2018;33:1-5
|How to cite this URL:|
Thakral P, Jyotsna, Tandon P, Dureja S, Pant V, Sen I. Radiation dose to the occupational worker during the synthesis of 188Re-labeled radiopharmaceuticals in the nuclear medicine department. Indian J Nucl Med [serial online] 2018 [cited 2018 Aug 20];33:1-5. Available from: http://www.ijnm.in/text.asp?2018/33/1/1/223251
| Introduction|| |
Rhenium-188 (188 Re) is a generator produced beta-emitting radioisotope which has shown utility for a variety of therapeutic applications in nuclear medicine.188 Re is obtained from 188 W/188 Re generator and decays with a half-life of 17 h which is long enough for the therapeutic purpose and short enough to give extra radiation high energy β– burden. It emits both a gamma photon (Eγ = 155 keV) which is easily collimated by a low-energy collimator and a beta particle with the maximum energy Eβmaximum of 2.11 MeV (average range in soft tissue-3 mm) which is well suited for treating solid tumors. These favorable physical and radiation characteristics, easy logistics, and availability in a pyrogen and carrier free state have made it suitable option for clinical use. At our center, at the Fortis Memorial Research Institute (FMRI), Gurgaon, we are routinely synthesizing Re-188 labeled radiopharmaceuticals such as 188 Re-hydroxyl- ethylidene -diphosphonate(HEDP),188 Re-4- hexadecyl -1, 2, 9,9-tetramethyl-4, 7-diaza-1, 10-decanethiol (HDD)/lipiodol and 188 Re-tin colloid for bone pain palliation, hepatocellular carcinoma treatment and radio synovectomy, respectively.
Estimation of exposure to the occupational staff involved in the synthesis of radiopharmaceuticals, dose administration, and scan acquisition was thought to be essential as a part of radiation safety practice. In view of the potential hazard associated with the ionizing radiation, these practices are subject to regulatory control. Several national and international regulatory authorities have laid down safe radiation work practices and permissible radiation exposure limits. The government of India provides the statutory basis in the form of Atomic Energy Act 1962, and the rules are promulgated by the Atomic Energy Regulatory Board (AERB). According to ICRP recommendations 103 (2007), any person handling radiation and likely to receive an occupational radiation exposure of more than 1 mSv is liable to be monitored and the equivalent radiation dose to personnel should not exceed 20 mSv/year averaged over 5 years, not exceeding 50 mSv in any year, but the upper limit is 30 mSv according to AERB in India.
With the multifarious application of 188 Re-labeled products, monitoring radiation exposure to the radiopharmacist involved become a prime concern. The objectives of the present study hence were to assess the whole-body radiation doses received by radio pharmacists while synthesizing 188 Re-labeled products and to compare the occupational burden with the dose limits recommended by AERB, India.
| Materials and Methods|| |
A 1850MBq 188 W-188 Re generator was procured from ITG, Germany. The generator was eluted as and when required to obtain Na 188 ReO4- in a pyrogen and carrier free form.
Dosimeter and readout system
A digital pocket dosimeter (MyDose Mini – G 9679) was obtained from ALOKA to measure the dose received. The dosimeter was calibrated by Nuvia India in January 2017. The applied radionuclide for calibration was Co-60. The applied dose was 19.834, and the background subtracted observed reading was 18.498 which showed a relative intrinsic error of − 6.74%. A survey meter (Inspector – SN# 28592) was used for the general survey. It was also calibrated by Nuvia India in January 2017. It was also calibrated by Co-60 and showed a relative intrinsic error of 10%–13% at different applied exposure rate.
The precursors used in the synthesis of 188 Re-labeled HDD/Lipiodol were obtained from ABX GmbH, Germany, and HEDP kit was obtained from Polatom. All other reagents used in labeling were of analytical grade.
Synthesis of Re-188 labeled HDD/Lipiodol, HEDP and tin colloid was carried out by designated skilled personnel at the radiopharmacy laboratory of the Department of Nuclear Medicine, FMRI, Gurgaon, Haryana, India. Radiopharmacist stood behind the L-bench during preparation with a lead equivalent glass insert and took care of the three cardinal principles of radiation safety and followed the time, distance, and shielding approach to minimize the radiation exposure. Data were collected for 6 syntheses of 188 Re-HDD/Lipiodol, 4 for 188 Re-HEDP, and 3 for 188 Re-tin colloid followed by the quality control procedure.
A survey meter (Inspector) was used to measure the radiation level in the radiopharmacy laboratory before the start of labeling procedure by keeping it at the location where the radiopharmacist normally stands during preparation. The radiation survey meter was calibrated at the accredited laboratory Nuvia (India). The survey meter was also checked periodically for its accuracy by measuring the exposure rate at 2 meters from the known activity of I-131. The pocket dosimeter (MyDose mini-ALOKA) was given to the radiopharmacist performing the labeling of Re-188 labeled compounds which was placed at chest level. All radiopharmaceuticals were synthesized by a single radiopharmacist to avoid any operator discrepancy. Radiopharmacist performed three steps of task in the preparation Re-188 pharmaceuticals. The first step was the elution of activity from the generator. It was done with three different volumes of saline - 2 ml, 1.5 ml, and then 2.5 ml. The first sample of 2 ml was usually discarded and then, the remaining activity was used according to the requirement. The total amount of radioactivity handled during labeling and the duration of each labeling procedure was noted. The second step was to perform the labeling according to the protocols which involves mixing, heating, and finally, the dose dispensing. The third step was to perform the quality control procedures. Radiochemical purity was determined by thin layer chromatography using different solid and mobile phases. The total radiation dose received by the radiopharmacist was timed from the first step and ending when the radiopharmacist finally prepared the dose for injection. The amount of activity eluted and the dose received during elution was also noted separately as the amount of activity eluted and used for synthesis was sometimes different. The radiation doses received by the radiopharmacist were read directly from the dosimeter and time and dose for each step was recorded.
For 188 Re-HEDP, 2960–3700 MBq (80–100 mCi) ReO4- in 1–2 ml was added to the cold kit and the reconstituted solution was then heated in boiling water for 25 min. After heating, the solution was allowed to cool at room temperature and following that 2 ml of acetate buffer were added. Radiochemical purity was determined using Whatman paper no. 1 as solid phase and saline and acetone as mobile phases. The percentages of different entities were determined and a labeling efficiency of >95% was ensured before intravenous injection into the patient.
For 188 Re-HDD/Lipiodol, 3700–4440 MBq (100–120 mCi) ReO4- in 1–2 ml was added to the HDD kit and vortexed for 5 min. The mixture was heated in water bath at 100°C for 60 min. Following heating, 3 ml Lipiodol was added to the vial and vortexed again for 10 min. The resulting solution was then centrifuged at 300 rpm for 10 min to separate the aqueous and organic layer. Finally, the aqueous layer was removed, and 188 Re-Lipiodol was harvested. If required, more Lipiodol was added and the whole procedure of mixing, centrifugation, and separation were followed. For quality control, the same protocol was followed as that of 188 Re-HEDP.
For 188 Re-Tin colloid, 0.5 ml of required amount of 188 ReO4- (370–740MBq, 10–20 mCi) was added into a clean vial containing 0.5 ml of freshly prepared stannous chloride solution. The solution was mixed well and heated at 100°C for 2 h. After cooling, required amount of 0.2 M phosphate buffer was added to adjust the pH of the final solution to 8. For quality control, the thin-layer chromatography silica gel (ITLC) strip with the sample was developed in saline and activity associated with each segment was determined.
Descriptive statistical analysis was performed for the collected data; and mean, median, standard deviation (SD), and range (minimum to the maximum value) were determined. All the readings were expressed as mean ± SD.
| Results|| |
The readings of the survey meter were 0.03 ± 0.01 mSv/h in the radiopharmacy laboratory. The survey meter was found to be accurate as the exposure rate at 2 m from 1 mCi of I-131 was 0.62 mR/h (i.e., within 20% of the expected value [0.55 mR/h]). The generator was eluted thirteen times during its shelf life and the radiation dose received during elution was assessed in the study [Figure 1]. The amount of 188 ReO4- used for labeling with HDD/Lipiodol, HEDP, and Tin colloid was in the range of 3182–4440 MBq, 2812–3774 MBq, and 962–1295 MBq, respectively. The radiation dose received during eluting the generator was in the range of 7–16 μSv [Table 1]. The mean activity eluted from the generator was 4314 MBq (116 mCi) and the mean dose received during the elution was 11.5 μSv [Table 1]. The mean radiation dose recorded in synthesis of 188 Re-Lipiodol was 0.052 ± 0.004 mSv [Table 2],188 Re-HEDP was 0.009 ± 0.004 mSv [Table 3], and 188 Re-Tin colloid was 0.004 ± 0.001 mSv [Table 4]. Mean duration of labeling was 95 min, 40.5 min, and 131.5 min, respectively. The time required for quality control using ITLC for all the synthesis was same, i.e., 10 min and the mean radiation dose received during quality control was 3 μSv. However, the total dose received for all 13 procedures using 56 GBq (1516 mCi)188 ReO4- was 786 μSv acquired over a period of 6 months. The highest exposure was incurred in the synthesis of 188 Re-Lipiodol and the doses were highest during eluting the generator followed by the dose dispensing [Figure 2].
|Figure 1: Amount of activity eluted and the radiation dose received by the radiopharmacist during elution of the generator|
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|Figure 2: Comparison of activity handled, time utilized and the dose received by the radiopharmacist for different 188Re-radiopharmaceuticals|
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| Discussion|| |
The utility of Re-188 for treating various diseases has greatly increased by the development of an in-house 188 W/188 Re-generator by which Re-188 can be obtained in a carrier free state as Na 188 ReO4-. Parent radionuclide, tungsten-188 (W-188) has a half-life equal to 69.4 d and Re-188 has attractive physical and chemical properties by which it can be labeled to a variety of compounds for the diagnostic as well as therapeutic use. A1850 MBq (50 mCi) generator was procured in the department in FMRI and this study was conducted to determine the whole-body doses received by the personnel involved in the labeling of 188 Re-radiopharmacy, since there is paucity of literature regarding occupational exposure during synthesis of Re-188 radiopharmaceuticals. Three radiopharmaceuticals:188 Re-HEDP,188 Re-Lipiodol, and 188 Re-Tin colloid were synthesized over the shelf life of the generator. Andreeff et al. in a study measured the dose received by the radiochemist involved in the labeling of 188 Re-Labeled pharmaceuticals using ring dosimeters. They revealed that the true radiation dose to the skin of the fingertips exceeds by far the readings of the official ring dosimeters as well as the continuously readable beta- and gamma-dosimeters. They also suggested risk in exceeding the radiation limit of 500 mSv/a given in the German Radiation Protection Law (section sign 5).
The study results showed that the labeling of 188 Re-Lipiodol yielded the highest mean radiation dose of 0.052 ± 0.01 mSv, followed by 188 Re-HEDP of 0.009 ± 0.002 mSv, whereas the dose from the labeling of 188 Re-Tin colloid was the lowest 0.004 ± 0.0006 mSv. It was observed that the time for which the activity manipulation was done with the hands was highest for 188 Re-Lipiodol followed by the same time for 188 Re-HEDP and 188 Re-Tin colloid. Furthermore, the highest amount of activity was handled for 188 Re-Lipiodol followed by 188 Re-HEDP and the lowest for 188 Re-Tin colloid. The two parameters which were found crucial for the observed trend were the time for which the radioactivity is handled and amount of the activity handled during the radiolabelling procedures. Higher the both, higher is the radiation exposure.Furthermore, the doses received by the radiopharmacist were higher during elution. The activity eluted in the initial days was higher than on the days nearing the end of shelf life as is observed with other generator systems.
Another parameter that could be crucial for the dose received by the occupational worker is how proficient or dexterous is the radiopharmacist in handling the radioactivity. The doses can be different for different workers depending on the level of their expertise to handle radioactivity. In this study, it was ensured that only the trained staff was involved and also, all the labeling procedures were carried by the single radiopharmacist to minimize the interpersonnel differences. Same pocket dosimeter was assigned every time during the labeling procedure to rule out the error from different devices.
The mean whole-body dose received by the radiopharmacistin thirteen radiolabeling procedures (Lipiodol-6, HEDP-4, Tin colloid-3) was found to be 0.025 mSv in 6 months. This dose received by a single radiopharmacist, over a period of 6 months at the current frequency was far below the occupational limits. However, the total dose received by the radiopharmacist in handling a total of 56 GBq in all the 13 synthesis of the three radiopharmaceuticals was 0.786 mSv. These results leave us with greater flexibility to handle much higher activity for much longer time. If we assume double the number of synthesis per 6 months (24 synthesis/year) and that too of 188 Re-Lipiodol, since the highest mean exposure (0.052 mSv) was obtained during the synthesis of 188 Re-HDD/Lipiodol, the doses to the personnel involved in a year will be 1.248 mSv. The readings of the chest TLD badge and the wrist TLD badge of the worker for the cumulative Re-188 radiopharmacy as well as the other departmental work during this period of 6 months was 0.5 mSv and 0.6 mSv, respectively. This reading was well within the permissible limits and insignificantly higher to the doses received by the worker with routine departmental work alone. Although the doses received were far below the limits, the radiation workers were advised to follow ALARA principle and it was suggested that trained occupational workers should work on rotation. The regular use of radiation monitoring devices such as the pocket dosimeters and TLD badges was encouraged, and radiation surveys were conducted routinely in the department.
The present study has certain limitations. First, we measured whole-body doses in regard to Re-188 manipulation but could not measure the extremity doses. Second, a small number of whole-body measurements could be taken due to the limited number of patients were available during the shelf life of the generator.
| Conclusion|| |
This study confirmed that the synthesis of 188 Re-radiopharmacy is safe and the whole-body radiation doses received by personnel involved in the radio-labeling procedures were within recommended safety levels of occupational dose limits of AERB, i.e., 20 mSv/year (averaged over 5 years).
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4]