Development of 99m Tc production from (n,γ) 99 Mo

Transcription

1 Development of m Tc production from (n,γ) Mo M. TANASE *1, T. SHIINA *1, A. KIMURA *2, K. NISHIKATA *2, S. FUJISAKI *1, A. OHTA *1, M. KOBAYASHI *3, A.YAMAMOTO *3, Y.KAWAUCHI *1, K. TSUCHIYA *2, N. TAKEUCHI *1, H. KAWAMURA *2 *1 Chiyoda Technol Corporation *2 Japan Atomic Energy Agency *3 FUJIFILM RI Pharma Co., Ltd.

2 Contents 1. Introduction 2. In the last study (1/2) 3. In the last study (2/2) 4. Purposes in the present study 5. Flow of experimental procedures 6. Goals of the tests 7. Procedures (1/2) 8. Procedures (2/2) 9. Inspection of product 10. Result 1 Recovery of Re 11. Result 2-1 Impurity of Mo in product 12. Calculation of Impurity ratio of Mo/ m Tc in product 13. Result 2-2 Impurity of MEK in product 14. Conclusion

3 Introduction m Tc is used as a radiopharmaceutical in the medical field for the diagnosis, and manufactured from Mo, the parent nuclide. Chiyoda Technol Corporation (CTC), Japan Atomic Energy Agency (JAEA) and FUJIFILM RI Pharma Co., Ltd. (FRI) have developed a (n, γ) Mo method to produce Mo, as a part of the industrial use expansion after JMTR will restart. However, the radioactive concentration of m Tc in the solution by the (n, γ) Mo method is greatly lower than that by the (n, f) Mo method. To overcome the difficulty, the solvent extraction of m Tc produced from Mo were done and followed by an alumina column method. 1

4 In the last study (1/2) Dissolution of MoO 3 Extraction of Re with MEK Purification with Basic-alumina column Adsorption to acidicalumina column Elution of Re with Saline A method shown in left side of this slide was proposed and, by using Re* instead of m Tc, Re recovery tests were tried in order to ascertain that the method is applicable to the commercial production of m Tc created from (n,γ) Mo. (* Re and Tc are homologous element) The purposes of the tests were as follows: (i)re recovery yield is more than 80%. (ii)the Re concentration factor, concentration of Re in saline to that of Re in Re-Mo solution, is more than 15. 2

5 In the last study (2/2) We got the following results: To dissolve MoO 3, 6M NaOH solution was chosen. Re was recovered with a yield of more than 90%, and cleared our goal of 80%. By column method using basic and acidic alumina columns, Re was recovered successfully with the concentration factor of 33, and cleared our goal of 15. These results show that it is possible to obtain the high concentration of m Tc by the solvent extraction with MEK, followed by alumina column method. 3

6 Purposes in the present study In the present study, the process from extraction of Re to elution of Re was repeated in order to simulate milking using the same Mo-Re solution, and (i) Effect of milking to recovery yields was examined. And also, (ii) Impurities of Mo and MEK in the product were determined and compared with the tentative limits of regulations in Japan, respectively. 4

7 Goals of the tests In order to make sure adaptable to the practical production, effect of milking to recovery yields, Re concentration factors, and impurities of product were examined. The goals of the tests were as follows: (i) Re recovery yields are more than 80%. (ii) The Re concentration factor, concentration of Re in saline to that of Re in Re-Mo solution, is more than 15. (iii) The impurities of Mo and MEK in product are below the tentative limits of regulations in Japan. 5

8 Flow of Experimental Procedures Extraction of Re Milking (Extraction) process: The aqueous phase of Mo-solution was subjected to the extraction process from Addition of Re to Mo-solution to Inspection of product by five times. Dissolution of MoO 3 Addition of Re to Mo-solution Extraction of Re with MEK Purification and concentration of Re Separation of Organic and Aqueous phases Aqueous phase Organic phase Organic phase Purification with Basic-alumina column Adsorption to acidic-alumina column Elution of Re with Saline Inspection of product 6

9 Procedures(1) Extraction of Re Milking was repeated five times: 1 st day, 2 nd day, 3 rd day, 8 th day and 9 th day. Mo/Re solution Extraction of Re with MEK 6M-NaOH :400ml MoO 3 :200g Re : 428μg ( m Tc estimated : 339Ci) MEK after separation Next step MEK : 90ml Mixing time: 5min Standing time : 30min Purification and concentration of Re After separation, aqueous phase was kept at 30 C in water bath. :Re :Mo 7

10 Procedures(2) Purification and Concentration of Re MEK 1 st column Basic Alumina:7g 12 mm I.D. 2 nd column Acidic Alumina:7g 12 mm I.D. 1 st column was used for removing Mo and H 2 O from MEK, and 2 nd column for adsorbing Re. MEK Containing Re Basic alumina Acidic alumina Product of Re Distilled water 30ml 2 nd column Acidic Alumina 12 mm I.D. In order to rinse MEK remaining in 2 nd column, distilled water was passed. Saline 6ml (discarded) + 16ml (Re was collected) 2 nd column Acidic Alumina 12 mm I.D. Distilled water 8

11 Inspection of product Impurities of Mo and MEK in the product were determined by ICP-AES and HPLC. From the impurity of Mo, the radioactivity of Mo was calculated under the conditions of practical production and the radioactive impurity percent of Mo/ m Tc was estimated. And the values determined were compared with tentative ones regulated in radiopharmaceuticals and shown below. Quality levels Radioactive impurity Mo/ m Tc Ratio(estimated) 0.015% Chemical impurity Permissible amount of MEK:5000ppm 9

12 Re recovery yield (%) Recovery yields Result 1 Recovery of Re Experimental result on recovery yields is shown. Effect of milking to recovery yields was examined After the first 6 ml of saline was discarded, Re was collected in the next 16 ml of saline as a product at a flow rate of about 10 ml/min. 0 1st (1 Day) 2nd (2 Day) 3rd (3 Day) Milking 4th (8 Day) 5th (9 Day) The average recovery yield was very high to be 98.1%, and the concentration factor

13 Ratio to 0.015% Amount of Mo (ppm) Results 2-1 Impurity of Mo in product Amount of Mo in Re product :Amount of Mo in the product The impurity of Mo was ppm (16 ml) and the percent ratio of Mo in the product to Mo in the original Re-Mo solution was 4.0x10-7 %. From this value, the impurity of Mo/ m Tc was estimated below. 0 1st (1 Day) 2nd (2 Day) 3rd (3 Day) Milking 4th (8 Day) 5th (9 Day) Mo/ m Tc in m Tc product And ratio (Estimation) Mo/ m Tc (%) 9.E-07 8.E-07 7.E-07 6.E-07 5.E-07 4.E-07 3.E-07 2.E-07 1.E-07 0.E+00 1st (1 Day) :impurity of Mo in the product (left scale) :ratio to 0.015% (right scale) 2nd (2 Day) 3rd (3 Day) Milking 4th (8 Day) 5th (9 Day) 6.E-03 5.E-03 4.E-03 3.E-03 2.E-03 1.E-03 0.E+00 The impurity of Mo/ m Tc was calculated to be 5.0x10-7 %* which was much less than 0.015% of the regulation limit. *The calculation was shown in the next slide. 11

14 Calculation of impurity ratio of Mo/ m Tc in product Irradiation of MoO 3 Target MoO 3 : 200 g (Mo:133 g) Irradiation : 6 days in JMTR Radioactivity produced: 23.9 TBq (646 Ci) of Mo Dissolution of MoO 3 Extraction of m Tc with MEK Purification with Basic-alumina column Adsorption to acid-alumina column Elution of m Tc with Saline Inspection of product Dissolution of target: 400 ml of 6M NaOH, (volume becomes 470 ml) Extraction of m Tc, 2 days later 14.1 TBq(381 Ci) of Mo(Specific Activity : 2.86 μci/μgmo), 12.5 TBq(339 Ci) of m Tc Radioactivity of Mo in product is 1.52 μci. Impurity of Mo/ m Tc is calculated to be 5.0 x10-7 % using these Elution: 0.9% NaCl solution values. (16 ml) Concentration of product: 700 GBq (19 Ci) /ml Impurity of Mo: ppm 0.53 μgmo Impurity of Mo/ m Tc was estimated to be 5.0x10-7 %. Impurity of MEK is about 600 ppm. 12 1

15 Amount of MEK (ppm) Percent ratio to 5000 ppm Results 2-2 Impurity of MEK in product Amount of MEK :amount of MEK (ppm) (left scale) :percent ratio to 5000 ppm (right scale) As shown in the figure, the amount of MEK in the product was increasing with elapsed day st (1 Day) 2nd (2 Day) 3rd (3 Day) Milking 4th (8 Day) 5th (9 Day) Permissible amount of MEK: 5000ppm Average impurity of MEK was 572 ppm and about 1 order lower than 5000 ppm of regulation in Japan. 13

16 Conclusion The results are concluded below; (i) Recovery yield The average recovery yield was 98.1%, and the concentration factor 29, which was beyond our goal of 15. The concentration of m Tc was estimated to be 700 GBq (19 Ci) /ml when 200 g of MoO 3 to be irradiated in JMTR and 12.5 TBq(339 Ci) of m Tc are handled. (ii) Impurities of Mo and MEK Impurity of Mo was ppm and the percent ratio of Mo/ m Tc in the product was calculated to be 5.0x10-7 %, when 200 g of MoO 3 and 12.5 TBq(339 Ci) of m Tc are handled. The value of 5.0x10-7 % was 3 orders lower than that of tentative regulation limit in Japan. The average impurity of MEK was 572 ppm, and about 1 order lower than that of tentative regulation limit in Japan. Following these results, we have been developing the production method using Mo / m Tc under the cooperation of BATAN in Indonesia. 14

17 Thank you for your attention

18 What is the total number of m Tc and Tc produced in a day from 3.7TBq (100 Ci ) of Mo? 3.7TBq (100 Ci ) Mo The number of Mo is 1.27x Calculation of Re weight (1/2) 1 day later 66 hrs (87.7%) (12.3%) m Tc 6.0 hrs Tc 2.1x10 5 years (ignored) The number of Mo decayed in a day is 2.83x TBq (77.7 Ci) Mo The number of Mo is 9.86x The number is equal to the total number of m Tc and Tc, when the decay of Tc is ignored. Mo Decayed = ( m Tc + Tc) produced

19 Calculation of Re weight (2/2) How much is the weight of Re equivalent to sum of m Tc and Tc produced in a day from 3.7TBq (100 Ci) of Mo? 3.7TBq (100 Ci ) Mo The number of Mo is 1.27x day later 2.9TBq (77.7 Ci ) Mo The number of Mo is 9.86x hrs (87.7%) (12.3%) m Tc 6.0 hrs Tc 2.1x10 5 years (ignored) Mo Decayed = ( m Tc + Tc) produced = 2.83x10 17 Weight of 2.83x10 17 Re atoms is 87 μg. From this result, 428 μg is corresponding to the number of Tc which 18.2 TBq(492 Ci) of Mo decays in a day, while the amount of m Tc produced is calculated to be 12.6 TBq(339 Ci).

20 Procedures of this method and specification of the product Irradiation of MoO 3 Dissolution of MoO 3 Target MoO 3 : 200 g Irradiation : 6 days in JMTR Radioactivity produced: 23.9 TBq (646 Ci) of Mo Dissolution of target: 400 ml of 6M NaOH, (volume becomes 470 ml) Extraction of m Tc with MEK Purification with Basic-alumina column Two days later, Extraction of m Tc : 14.1 TBq(381 Ci) of Mo, 12.5 TBq(339 Ci) of m Tc Purification: 7 g of Basic Alumina(12 mmφ) Adsorption to acid-alumina column Adsorption: 7 g of Acidic Alumina (12 mmφ) Elution of m Tc with Saline Inspection of product Elution: 0.9% NaCl solution(16 ml) Recovery of m Tc: 98%, 12.3TBq(332 Ci) Processed time: 1 hr.(10% of m Tc will decay) Concentration of product: 700 GBq (19 Ci) /ml Impurity of Mo/ m Tc is 5.0x10-7 %, Impurity of MEK is about 600 ppm.