ارزیابی اکتیویته ویژه لوتسیوم-177 تولیدی به دو روش مستقیم و غیرمستقیم با استفاده از رآکتور تحقیقاتی تهران

شیروانی آرانی, سیمیندخت; بهرامی سامانی, علی; قنادی مراغه, محمد

doi:10.24200/nst.2023.1328

نوع مقاله : مقاله پژوهشی

نویسندگان

پژوهشکده چرخه سوخت هسته‌ای، پژوهشگاه علوم و فنون هسته‌ای، سازمان انرژی اتمی ایران، صندوق پستی: 8486-11365، تهران- ایران

https://doi.org/10.24200/nst.2023.1328

چکیده

در پژوهش حاضر به بررسی امکان تولید رادیونوکلید لوتسیوم-177، Lu¹⁷⁷، در رآکتور تحقیقاتی تهران، TRR، پرداخته شده است. Lu¹⁷⁷ با داشتن ویژگی‏های واپاشی هسته‏ای مناسب و هم‏چنین رفتار شیمیایی مطلوب، یک رادیونوکلید ایده‏آل جهت تهیه رادیوداروهای درمانی است. برخی از رادیوداروهای حاوی Lu¹⁷⁷ در حال حاضر در کشور در درمان انواع سرطان استفاده می‏شود و بسیاری از آنها تحت آزمایشات بالینی هستند. رادیونوکلید Lu¹⁷⁷ را می‏توان یا مستقیماً از طریق واکنش Lu¹⁷⁷Lu(n,γ)¹⁷⁶ یا به طور غیرمستقیم طی واکنش تولید کرد. بازده پرتودهی Lu¹⁷⁷ در هر دو مسیر تولید به صورت تجربی در 14 روز تابش در شار نوترونی حرارتی ^1-s ^2-cm 10¹³×5، تعیین شده و با محاسبات نظری مربوطه مقایسه شد. اثر شار نوترون حرارتی بالاتر و هم‏چنین کاهش درصد غنیسازی Yb¹⁷⁶ بر تغییرات اکتیویته / اکتیویته ویژه حاصل، با استفاده از نرمافزار متلب به صورت تئوری مورد بررسی قرار گرفت. مشخص شد در هر دو روش تولید، شار نوترون بالاتر منجر به تولید اکتیویته / اکتیویته ویژه بالاتر می‏شود. با این‏حال، هیچ تأثیری بر سرعت افت اکتیویته ویژه طی دو هفته پس از پایان پرتودهی ندارد. به‏علاوه استفاده از ایتربیم-176 با غنای پایین‏تر در روش غیرمستقیم، منجر به کاهش اکتیویته ویژه سریعتر طی دو هفته پس از پایان پرتودهی می شود.

کلیدواژه‌ها

20.1001.1.17351871.1402.44.1.11.1

عنوان مقاله [English]

Evaluation of the produced 177Lu-specific activity via direct and indirect methods using Tehran Research Reactor

نویسندگان [English]

S. Shirvani Arani
A. Bahrami - Samani
M. Ghannadi - Maragheh

Nuclear Fuel Cycle Research School, Nuclear Science and Technology Research Institute, AEOI, P.O.Box:11365-8486, Tehran-Iran

چکیده [English]

The present research investigates the feasibility of producing the radionuclide Lutetium-177 (¹⁷⁷Lu) at the Tehran research reactor, TRR. ¹⁷⁷Lu, with suitable nuclear decay characteristics and good chemical behavior, is an ideal therapeutic radionuclide. Some ¹⁷⁷Lu-containing radiopharmaceuticals are currently applied in the treatment of various cancers, and many are under development and being tested in clinical trials in Iran. The radionuclide ¹⁷⁷Lu can be produced either directly by the ¹⁷⁶Lu (n,γ)¹⁷⁷Lu reaction or indirectly by the reaction. The irradiation yield of ¹⁷⁷Lu in both production routes was experimentally determined for 14 days at a thermal neutron flux of 5×10¹³ cm^-2.s^-1 and was compared with the theoretical calculations. The effects of higher neutron fluxes and a reduction in 176Yb-enrichment-percentage on the produced activity/specific activity variations were assessed theoretically using MATLAB software. It was found that higher neutron fluxes led to higher activity. However, it does not impact specific activity fall rates two weeks after the end of the bombardment. In addition, a lower enrichment percentage of the target material utilized in the indirect method leads to a faster specific activity fall two weeks after the end of the bombardment.

کلیدواژه‌ها [English]

Lutetium-177
Specific activity
Carrier added
Non carrier added
Tehran Research Reactor

مراجع

1. S. Shirvani Arani, M. Ghannadi-Maragheh, Translation of the book Chemistry and Analysis of Radionuclides, Laboratory Methods and Teaching Methods, Published by the Research Institute of Nuclear Sciences and Technologies, Iran, (2013) (In Persian).

2. T. Das, S. Banerjee, Theranostic Applications of Lutetium-177 in Radionuclide Therapy, Curradiopharm, 9(1), 94-101 (2016).

3. W.A. Müller, U. Linzner, E.H. Schäffer, Organ distribution studies of lutetium-177 in mouse, Int J Nucl Med Biol., 5(1), 29 (1978).

4. A. Ando, et al, ¹⁷⁷Lu-EDTMP: a potential therapeutic bone agent, Nucl Med Commun, 19(6), 587 (1998).

5. R.F. Meredith. et al., Intraperitoneal radioimmunotherapy of ovarian cancer with lutetium-177-CC49, J. Nucl. Med., 37(9), 1491 (1996).

6. J. Strosberg, et al., Phase 3 Trial of ¹⁷⁷Lu-Dotatate for Midgut Neuroendocrine Tumors, N. Engl. J. Med., 376(2), 125 (2017).

7. MED raysintell Nuclear Medicine Report and Directory, Edition (2019).

8. K. Herrmann, et al, Radiotheranostics: a roadmap for future development, Lancet Oncol., 21, e146 (2020).

9. A. Bahrami-Samania, et al., Production, Quality Control and Pharmacokinetic Studies of ¹⁷⁷Lu-EDTMP for Human Bone Pain Palliation Therapy Trials, Iran J Pharm Res, 11(1), 137 (2012).

10. H. Yousefnia, et al., Preparation and quality control of ¹⁷⁷Lu-[tris(1,10-phenanthroline) lutetium(III)] complex for therapy, Nuclear Med Rev., 13, 49 (2010).

11. H. Yousefnia, et al., Preparation and quality control of lutetium-177 bleomycin as a possible therapeutic agent, NUKLEONIKA, 55(3), 285 (2010).

12. H. Yousefnia, et al, Development of ¹⁷⁷Lu-DOTA-anti-CD20 for radioimmunotherapy, J. Radioanal. Nucl. Chem., 287, 199 (2011).

13. H. Yousefnia, et al, Development of ¹⁷⁷Lu-phytate Complex for Radiosynovectomy, Iran J Basic Med Sci., 16, 705 (2013).

14. S. Zolghadri, et al., Production, biodistribution assessment and dosimetric evaluation of ¹⁷⁷Lu-TTHMP as an agent for bone pain palliation, Asia Oceania J Nucl Med Biol., 3(1), 35 (2015).

15. H. Yousefnia, et al., Absorbed dose assessment of ¹⁷⁷Lu-zoledronate and ¹⁷⁷Lu-EDTMP for human based on biodistribution data in rats, Journal of Medical Physics, 40, 102 (2015).

16. A. Fakhari, et al., Radiolabeling and evaluation of two ¹⁷⁷Lu-labeled bis-phosphonates, Iran J Nucl Med., 23, 108 (2015).

17. H. Yousefnia, et al., Estimated human absorbed dose of ¹⁷⁷Lu–BPAMD based on mice data: Comparison with ¹⁷⁷Lu–EDTMP, Appl Radiat Isot., 104, 128 (2015).

18. H. Yousefnia, et al, Preparation and biodistribution assessment of low specific activity ¹⁷⁷Lu-DOTATOC for optimization studies, Iran J Nucl Med., 24(2), 85 (2016).

19. N. Salek, et al, Comparative studies of extraction chromatography and electro-amalgamation separation to produce no-carrier added ¹⁷⁷Lu by Tehran research reactor, Iran J Nucl Med., 25(1), 23-33 (2017).

20. N. Salek, et al, Production of ¹⁷⁷Lu in No Carrier Added, J. of Nucl Sci. and Tech., 77, 1-8 (2016).

21. A. Dash, et al, Production of ¹⁷⁷Lu for Targeted Radionuclide Therapy: Available Options, Nucl Med Mol Imaging., 49, 85 (2015).

22. IAEA Medical Isotope Browser, https://www-nds. Iaea.org/relnsd/isotopia/isotopia.html.

مجله علوم، مهندسی و فناوری هسته‌ای

ارزیابی اکتیویته ویژه لوتسیوم-177 تولیدی به دو روش مستقیم و غیرمستقیم با استفاده از رآکتور تحقیقاتی تهران

مراجع

مراجع

1. S. Shirvani Arani, M. Ghannadi-Maragheh, Translation of the book Chemistry and Analysis of Radionuclides, Laboratory Methods and Teaching Methods, Published by the Research Institute of Nuclear Sciences and Technologies, Iran, (2013) (In Persian).

2. T. Das, S. Banerjee, Theranostic Applications of Lutetium-177 in Radionuclide Therapy, Curradiopharm, 9(1), 94-101 (2016).

3. W.A. Müller, U. Linzner, E.H. Schäffer, Organ distribution studies of lutetium-177 in mouse, Int J Nucl Med Biol., 5(1), 29 (1978).

4. A. Ando, et al, ¹⁷⁷Lu-EDTMP: a potential therapeutic bone agent, Nucl Med Commun, 19(6), 587 (1998).

5. R.F. Meredith. et al., Intraperitoneal radioimmunotherapy of ovarian cancer with lutetium-177-CC49, J. Nucl. Med., 37(9), 1491 (1996).

6. J. Strosberg, et al., Phase 3 Trial of ¹⁷⁷Lu-Dotatate for Midgut Neuroendocrine Tumors, N. Engl. J. Med., 376(2), 125 (2017).

7. MED raysintell Nuclear Medicine Report and Directory, Edition (2019).

8. K. Herrmann, et al, Radiotheranostics: a roadmap for future development, Lancet Oncol., 21, e146 (2020).

9. A. Bahrami-Samania, et al., Production, Quality Control and Pharmacokinetic Studies of ¹⁷⁷Lu-EDTMP for Human Bone Pain Palliation Therapy Trials, Iran J Pharm Res, 11(1), 137 (2012).

10. H. Yousefnia, et al., Preparation and quality control of ¹⁷⁷Lu-[tris(1,10-phenanthroline) lutetium(III)] complex for therapy, Nuclear Med Rev., 13, 49 (2010).

12. H. Yousefnia, et al, Development of ¹⁷⁷Lu-DOTA-anti-CD20 for radioimmunotherapy, J. Radioanal. Nucl. Chem., 287, 199 (2011).

13. H. Yousefnia, et al, Development of ¹⁷⁷Lu-phytate Complex for Radiosynovectomy, Iran J Basic Med Sci., 16, 705 (2013).

14. S. Zolghadri, et al., Production, biodistribution assessment and dosimetric evaluation of ¹⁷⁷Lu-TTHMP as an agent for bone pain palliation, Asia Oceania J Nucl Med Biol., 3(1), 35 (2015).

15. H. Yousefnia, et al., Absorbed dose assessment of ¹⁷⁷Lu-zoledronate and ¹⁷⁷Lu-EDTMP for human based on biodistribution data in rats, Journal of Medical Physics, 40, 102 (2015).

16. A. Fakhari, et al., Radiolabeling and evaluation of two ¹⁷⁷Lu-labeled bis-phosphonates, Iran J Nucl Med., 23, 108 (2015).

17. H. Yousefnia, et al., Estimated human absorbed dose of ¹⁷⁷Lu–BPAMD based on mice data: Comparison with ¹⁷⁷Lu–EDTMP, Appl Radiat Isot., 104, 128 (2015).

18. H. Yousefnia, et al, Preparation and biodistribution assessment of low specific activity ¹⁷⁷Lu-DOTATOC for optimization studies, Iran J Nucl Med., 24(2), 85 (2016).

19. N. Salek, et al, Comparative studies of extraction chromatography and electro-amalgamation separation to produce no-carrier added ¹⁷⁷Lu by Tehran research reactor, Iran J Nucl Med., 25(1), 23-33 (2017).

20. N. Salek, et al, Production of ¹⁷⁷Lu in No Carrier Added, J. of Nucl Sci. and Tech., 77, 1-8 (2016).

21. A. Dash, et al, Production of ¹⁷⁷Lu for Targeted Radionuclide Therapy: Available Options, Nucl Med Mol Imaging., 49, 85 (2015).

دوره 44، شماره 1 - شماره پیاپی 103
فروردین 1402
صفحه 87-96

ارزیابی اکتیویته ویژه لوتسیوم-177 تولیدی به دو روش مستقیم و غیرمستقیم با استفاده از رآکتور تحقیقاتی تهران

مراجع

مراجع

1. S. Shirvani Arani, M. Ghannadi-Maragheh, Translation of the book Chemistry and Analysis of Radionuclides, Laboratory Methods and Teaching Methods, Published by the Research Institute of Nuclear Sciences and Technologies, Iran, (2013) (In Persian).

2. T. Das, S. Banerjee, Theranostic Applications of Lutetium-177 in Radionuclide Therapy, Curradiopharm, 9(1), 94-101 (2016).

3. W.A. Müller, U. Linzner, E.H. Schäffer, Organ distribution studies of lutetium-177 in mouse, Int J Nucl Med Biol., 5(1), 29 (1978).

4. A. Ando, et al, 177Lu-EDTMP: a potential therapeutic bone agent, Nucl Med Commun, 19(6), 587 (1998).

5. R.F. Meredith. et al., Intraperitoneal radioimmunotherapy of ovarian cancer with lutetium-177-CC49, J. Nucl. Med., 37(9), 1491 (1996).

6. J. Strosberg, et al., Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors, N. Engl. J. Med., 376(2), 125 (2017).

7. MED raysintell Nuclear Medicine Report and Directory, Edition (2019).

8. K. Herrmann, et al, Radiotheranostics: a roadmap for future development, Lancet Oncol., 21, e146 (2020).

9. A. Bahrami-Samania, et al., Production, Quality Control and Pharmacokinetic Studies of 177Lu-EDTMP for Human Bone Pain Palliation Therapy Trials, Iran J Pharm Res, 11(1), 137 (2012).

10. H. Yousefnia, et al., Preparation and quality control of 177Lu-[tris(1,10-phenanthroline) lutetium(III)] complex for therapy, Nuclear Med Rev., 13, 49 (2010).

12. H. Yousefnia, et al, Development of 177Lu-DOTA-anti-CD20 for radioimmunotherapy, J. Radioanal. Nucl. Chem., 287, 199 (2011).

13. H. Yousefnia, et al, Development of 177Lu-phytate Complex for Radiosynovectomy, Iran J Basic Med Sci., 16, 705 (2013).

14. S. Zolghadri, et al., Production, biodistribution assessment and dosimetric evaluation of 177Lu-TTHMP as an agent for bone pain palliation, Asia Oceania J Nucl Med Biol., 3(1), 35 (2015).

15. H. Yousefnia, et al., Absorbed dose assessment of 177Lu-zoledronate and 177Lu-EDTMP for human based on biodistribution data in rats, Journal of Medical Physics, 40, 102 (2015).

16. A. Fakhari, et al., Radiolabeling and evaluation of two 177Lu-labeled bis-phosphonates, Iran J Nucl Med., 23, 108 (2015).

17. H. Yousefnia, et al., Estimated human absorbed dose of 177Lu–BPAMD based on mice data: Comparison with 177Lu–EDTMP, Appl Radiat Isot., 104, 128 (2015).

18. H. Yousefnia, et al, Preparation and biodistribution assessment of low specific activity 177Lu-DOTATOC for optimization studies, Iran J Nucl Med., 24(2), 85 (2016).

19. N. Salek, et al, Comparative studies of extraction chromatography and electro-amalgamation separation to produce no-carrier added 177Lu by Tehran research reactor, Iran J Nucl Med., 25(1), 23-33 (2017).

20. N. Salek, et al, Production of 177Lu in No Carrier Added, J. of Nucl Sci. and Tech., 77, 1-8 (2016).

21. A. Dash, et al, Production of 177Lu for Targeted Radionuclide Therapy: Available Options, Nucl Med Mol Imaging., 49, 85 (2015).

دوره 44، شماره 1 - شماره پیاپی 103فروردین 1402صفحه 87-96

4. A. Ando, et al, ¹⁷⁷Lu-EDTMP: a potential therapeutic bone agent, Nucl Med Commun, 19(6), 587 (1998).

6. J. Strosberg, et al., Phase 3 Trial of ¹⁷⁷Lu-Dotatate for Midgut Neuroendocrine Tumors, N. Engl. J. Med., 376(2), 125 (2017).

9. A. Bahrami-Samania, et al., Production, Quality Control and Pharmacokinetic Studies of ¹⁷⁷Lu-EDTMP for Human Bone Pain Palliation Therapy Trials, Iran J Pharm Res, 11(1), 137 (2012).

10. H. Yousefnia, et al., Preparation and quality control of ¹⁷⁷Lu-[tris(1,10-phenanthroline) lutetium(III)] complex for therapy, Nuclear Med Rev., 13, 49 (2010).

12. H. Yousefnia, et al, Development of ¹⁷⁷Lu-DOTA-anti-CD20 for radioimmunotherapy, J. Radioanal. Nucl. Chem., 287, 199 (2011).

13. H. Yousefnia, et al, Development of ¹⁷⁷Lu-phytate Complex for Radiosynovectomy, Iran J Basic Med Sci., 16, 705 (2013).

14. S. Zolghadri, et al., Production, biodistribution assessment and dosimetric evaluation of ¹⁷⁷Lu-TTHMP as an agent for bone pain palliation, Asia Oceania J Nucl Med Biol., 3(1), 35 (2015).

15. H. Yousefnia, et al., Absorbed dose assessment of ¹⁷⁷Lu-zoledronate and ¹⁷⁷Lu-EDTMP for human based on biodistribution data in rats, Journal of Medical Physics, 40, 102 (2015).

16. A. Fakhari, et al., Radiolabeling and evaluation of two ¹⁷⁷Lu-labeled bis-phosphonates, Iran J Nucl Med., 23, 108 (2015).

17. H. Yousefnia, et al., Estimated human absorbed dose of ¹⁷⁷Lu–BPAMD based on mice data: Comparison with ¹⁷⁷Lu–EDTMP, Appl Radiat Isot., 104, 128 (2015).

18. H. Yousefnia, et al, Preparation and biodistribution assessment of low specific activity ¹⁷⁷Lu-DOTATOC for optimization studies, Iran J Nucl Med., 24(2), 85 (2016).

19. N. Salek, et al, Comparative studies of extraction chromatography and electro-amalgamation separation to produce no-carrier added ¹⁷⁷Lu by Tehran research reactor, Iran J Nucl Med., 25(1), 23-33 (2017).

20. N. Salek, et al, Production of ¹⁷⁷Lu in No Carrier Added, J. of Nucl Sci. and Tech., 77, 1-8 (2016).

21. A. Dash, et al, Production of ¹⁷⁷Lu for Targeted Radionuclide Therapy: Available Options, Nucl Med Mol Imaging., 49, 85 (2015).

دوره 44، شماره 1 - شماره پیاپی 103
فروردین 1402
صفحه 87-96