تولید و کنترل کیفی رادیوداروی 175Yb-EDTMP برای تسکین درد متاستازهای استخوان

نوع مقاله: مقاله پژوهشی

نویسندگان

1 گروه مهندسی کاربرد پرتوها، دانشگاه شهید بهشتی، صندوق پستی: 1983963113، تهران- ایران

2 پژوهشگاه علوم و فنون هسته‌ای، سازمان انرژی اتمی ایران، صندوق پستی: 836-14395، تهران ـ ایران

3 گروه مهندسی پرتو پزشکی، دانشگاه شهید بهشتی، صندوق پستی: 1983963113، تهران ـ ایران

چکیده

متاستاز استخوان از عواقب اصلی برخی سرطان‌ها مثل سرطان پروستات، سینه و ریه است که با درد شدید استخوانی همراه است. رادیونوکلید 175Yb با نیم- عمر 4.18 روز و پرتو بتا با بیشینه انرژی 470 keV (86%)، پرتو گاما با فراوانی کم، و تولید آسان و ارزان جای­گزین مناسبی برای دیگر رادیونوکلیدها است. رادیونوکلید 175Yb در رآکتور تحقیقاتی 5MW تهران از طریق بمباران نوترونی 174Yb2O3 طبیعی تولید شد. خلوص رادیونوکلیدی 175Yb با استفاده از سیستم طیف‌سنج گامای مجهز به آشکارساز ژرمانیم فوق خالص با قدرت تفکیک بالا تعیین شد. ترکیب EDTMP با 175Yb در مدت یک ساعت، در دمای اتاق و در pH=8-9 نشان‌دار شد. کنترل کیفی و مطالعات توزیع زیست­‌شناختی
175Yb-EDTMPتهیه شده، بر روی موش صحرایی به انجام رسید. خلوص رادیوشیمیایی ترکیب حاصل با استفاده از کروماتوگرافی لایه­‌ی نازک بالغ بر بیش از 99% تعیین شد. نتایج به دست آمده، خصوصیات توزیع زیست­‌شناختی مناسبی را برای
 175Yb-EDTMP نشان داد که حاکی از تمرکز عمده­‌ی این رادیودارو در استخوان بود. این رادیودارو با گذشت 4 روز از دیگر اندام‌­ها
پاک­‌سازی شد. این پژوهش نشان داد که 175Yb-EDTMP یک رادیوداروی مناسب با نیم- عمر نسبتاً بالا و دز پایین برای تسکین درد متاستازهای استخوان است.

تازه های تحقیق

  1. A. N. Serafini, Therapy of Metastatic Bone Pain, Journal of Nuclear Medicine, 42 (6) (2001) 895.

 2.   D. Kardamakis, Bone Metastases: A Translational and Clinical Approach, (Springer Verlag 2009).

 3.   D. A. Casciato and M. C. Territo, Manual of clinical oncology, (Lippincott Williams & Wilkins 2008).

 4.   N. Pandit-Taskar, M. Batraki, C. R. Divgi, Radiopharmaceutical therapy for palliation of bone pain from osseous metastases, Journal of Nuclear Medicine, 45 (8) (2004) 1358-1365.

 5.   S. Chakraborty, T. Das, H. D. Sarma, M. Venkatesh, S. Banerjee, Comparative studies of 177Lu-EDTMP and 177Lu-DOTMP as potential agents for palliative radiotherapy of bone metastasis, Applied Radiation and Isotopes, 66 (9) (2008) 1196-1205.

 6.   W. A. Volkert and T. J. Hoffman, Therapeutic radiopharmaceuticals, Chemical Reviews, 99 (9) (1999) 2269-2292.

 7.   J. M. Jeong, Y. S. Choe, F. F. Knapp Russ, The WFNMB survey on the introduction of new radiopharmaceuticals for clinical research: Snapshot of the international perspective, World Journal of Nuclear Medicine, 6 (1) (2007) 52.

 8.   B. Ponsard, S. C. Srivastava, L. F. Mausner, F. F. Knapp, M. A. Garland, S. Mirzadeh, Production of Sn-117m in the BR2 high-flux reactor, Applied Radiation and Isotopes 67 (7-8) (2009) 1158-1161.

  1. L. Bodei, M. Lam, C. Chiesa, G. Flux, B. Brans, A. Chiti, F. Giammarile, EANM procedure guideline for treatment of refractory metastatic bone pain, European Journal of Nuclear Medicine and Molecular Imaging, 35 (10) (2008) 1934-1940.

 10. A. Bahrami-Samani, R. Bagheri, A. R. Jalilian, S. Shirvani-Arani, M. Ghannadi-Maragheh, M. Shamsaee, Production, Quality Control and Pharmacokinetic Studies of 166Ho-EDTMP for Therapeutic Applications, Scientia Pharmaceutica, 78 (3) (2010) 423.

 11.A. Bahrami-Samani, M. Ghannadi-Maragheh, A. R. Jalilian, M. Meftahi, S. Shirvani-Arani, S. Moradkhani, Production, Quality Control and Biological Evaluation of 153Sm-EDTMP in Wild-Type Rodents, Iranian Journal of Nuclear Medicine, 17 (2) (2009).

 12.B. Mathew, S. Chakraborty, T. Das, H. D. Sarma, S. Banerjee, G. Samuel, M. Venkatesh, M. R. A. Pillai, 175Yb labeled polyaminophosphonates as potential agents for bone pain palliation, Applied Radiation and Isotopes, 60 (5) (2004) 635-642.

 13.D. Máthé, L. Balogh, A. Polyák, R. Király, T. Márián, D. Pawlak, J. J. Zaknun, M. R. A. Pillai, G. A. Jánoki, Multispecies animal investigation on biodistribution, pharmacokinetics and toxicity of 177Lu-EDTMP, a potential bone pain palliation agent, Nucl. Med. Biol. 37 (2) (2010) 215-226.

 14.R. Chakravarty, T. Das, M. Venkatesh, A. Dash, An electro-amalgamation approach to produce 175Yb suitable for radiopharmaceutical applications, Radiochimica Acta (2012).

15.S. Senthamizhchelvan, R. F. Hobbs, H. Song, E. C. Frey, Z. Zhang, E. Armour, R. L. Wahl, D. M. Loeb, G. Sgouros, Tumor Dosimetry and Response for 153Sm-Ethylenediamine Tetramethylene Phosphonic Acid Therapy of High-Risk Osteosarcoma, Journal of Nuclear Medicine, 53 (2) (2012) 215-224.

 16.S. Chakraborty, P. R. Unni, M. Venkatesh, M. R. A. Pillai, Feasibility study for production of 175Yb: a promising therapeutic radionuclide, Applied Radiation and Isotopes, 57 (3) (2002) 295-301.

 17.S. C. Srivastava, The role of electron-emitting radiopharmaceuticals in the palliative treatment of metastatic bone pain and for radiosynovectomy: applications of conversion electron emitter Tin-117m, Brazilian Archives of Biology and Technology, 50 (SPE) (2007) 49-62.

 18.V. J. Lewington, Bone-seeking radionuclides for therapy, Journal of Nuclear Medicine, 46 (1 suppl) (2005) 38S-47S.

 19.S. W. Zielhuis, J. F. W. Nijsen, J. H. Seppenwoolde, B. A. Zonnenberg, C. J. G. Bakker, W. E. Hennink, P. P. Rijk, A. D. Schip, Lanthanide bearing microparticulate systems for multi-modality imaging and targeted therapy of cancer, Current Medicinal Chemistry-Anti-Cancer Agents, 5 (3) (2005) 303-313.

کلیدواژه‌ها


عنوان مقاله [English]

Production and Quality Control of 175Yb-EDTMP for Pain Palliation of Bone Metastases

نویسندگان [English]

  • L Safarzadeh 1
  • M Ghannadi-Maragheh 2
  • A Anvari 3
  • S. M.R Aghamiri 3
  • S Shirvani-Arani 2
  • A Bahrami-Samani 2
چکیده [English]

Bone metastasis is a major consequence of several cancers. The prostate, breast, lung cancers are mostly associated with the bone pain. Different radioisotopes are used for the bone pain palliation. 175Yb is proposed as a proper alternative to other radioisotopes due to its relatively long half-life (T1/2=4.18 days), maximum energy beta particle Eβ-=470 keV (86%), low abundance gamma emission, low cost, and easy production. In this study, 175Yb was obtained by thermal neutron bombardment of a natural 174Yb2O3 sample in the 5MW Tehran Research Reactor (TRR). The radionuclide purity of the 175Yb was ascertained by recording gamma ray spectra using a gamma spectrometer with a HPGe detector. Radiolabeling was completed in one hour by the addition of EDTMP at room temperature and pH=8-9. The quality control and biodistribution studies were carried out in normal wild-type rats. The radiochemical purity was determined by ITLC and the results were found to be higher than 99%. This study showed favorable biodistribution features of 175Yb-EDTMP which are indicating its significant accumulation in the bone. Also, it was observed that clearance of the activity from other organs accrued after 4 days. This research presents 175Yb-EDTMP as a suitable radiopharmaceutical with a proper half-life and low dose for the bone palliation of skeletal metastases.

کلیدواژه‌ها [English]

  • Bone metastases
  • 175Yb
  • Radiopharmaceutical
  • EDTMP
  • Biodistribution
  1. A. N. Serafini, Therapy of Metastatic Bone Pain, Journal of Nuclear Medicine, 42 (6) (2001) 895.

 2.   D. Kardamakis, Bone Metastases: A Translational and Clinical Approach, (Springer Verlag 2009).

 3.   D. A. Casciato and M. C. Territo, Manual of clinical oncology, (Lippincott Williams & Wilkins 2008).

 4.   N. Pandit-Taskar, M. Batraki, C. R. Divgi, Radiopharmaceutical therapy for palliation of bone pain from osseous metastases, Journal of Nuclear Medicine, 45 (8) (2004) 1358-1365.

 5.   S. Chakraborty, T. Das, H. D. Sarma, M. Venkatesh, S. Banerjee, Comparative studies of 177Lu-EDTMP and 177Lu-DOTMP as potential agents for palliative radiotherapy of bone metastasis, Applied Radiation and Isotopes, 66 (9) (2008) 1196-1205.

 6.   W. A. Volkert and T. J. Hoffman, Therapeutic radiopharmaceuticals, Chemical Reviews, 99 (9) (1999) 2269-2292.

 7.   J. M. Jeong, Y. S. Choe, F. F. Knapp Russ, The WFNMB survey on the introduction of new radiopharmaceuticals for clinical research: Snapshot of the international perspective, World Journal of Nuclear Medicine, 6 (1) (2007) 52.

 8.   B. Ponsard, S. C. Srivastava, L. F. Mausner, F. F. Knapp, M. A. Garland, S. Mirzadeh, Production of Sn-117m in the BR2 high-flux reactor, Applied Radiation and Isotopes 67 (7-8) (2009) 1158-1161.

  1. L. Bodei, M. Lam, C. Chiesa, G. Flux, B. Brans, A. Chiti, F. Giammarile, EANM procedure guideline for treatment of refractory metastatic bone pain, European Journal of Nuclear Medicine and Molecular Imaging, 35 (10) (2008) 1934-1940.

 10. A. Bahrami-Samani, R. Bagheri, A. R. Jalilian, S. Shirvani-Arani, M. Ghannadi-Maragheh, M. Shamsaee, Production, Quality Control and Pharmacokinetic Studies of 166Ho-EDTMP for Therapeutic Applications, Scientia Pharmaceutica, 78 (3) (2010) 423.

 11.A. Bahrami-Samani, M. Ghannadi-Maragheh, A. R. Jalilian, M. Meftahi, S. Shirvani-Arani, S. Moradkhani, Production, Quality Control and Biological Evaluation of 153Sm-EDTMP in Wild-Type Rodents, Iranian Journal of Nuclear Medicine, 17 (2) (2009).

 12.B. Mathew, S. Chakraborty, T. Das, H. D. Sarma, S. Banerjee, G. Samuel, M. Venkatesh, M. R. A. Pillai, 175Yb labeled polyaminophosphonates as potential agents for bone pain palliation, Applied Radiation and Isotopes, 60 (5) (2004) 635-642.

 13.D. Máthé, L. Balogh, A. Polyák, R. Király, T. Márián, D. Pawlak, J. J. Zaknun, M. R. A. Pillai, G. A. Jánoki, Multispecies animal investigation on biodistribution, pharmacokinetics and toxicity of 177Lu-EDTMP, a potential bone pain palliation agent, Nucl. Med. Biol. 37 (2) (2010) 215-226.

 14.R. Chakravarty, T. Das, M. Venkatesh, A. Dash, An electro-amalgamation approach to produce 175Yb suitable for radiopharmaceutical applications, Radiochimica Acta (2012).

15.S. Senthamizhchelvan, R. F. Hobbs, H. Song, E. C. Frey, Z. Zhang, E. Armour, R. L. Wahl, D. M. Loeb, G. Sgouros, Tumor Dosimetry and Response for 153Sm-Ethylenediamine Tetramethylene Phosphonic Acid Therapy of High-Risk Osteosarcoma, Journal of Nuclear Medicine, 53 (2) (2012) 215-224.

 16.S. Chakraborty, P. R. Unni, M. Venkatesh, M. R. A. Pillai, Feasibility study for production of 175Yb: a promising therapeutic radionuclide, Applied Radiation and Isotopes, 57 (3) (2002) 295-301.

 17.S. C. Srivastava, The role of electron-emitting radiopharmaceuticals in the palliative treatment of metastatic bone pain and for radiosynovectomy: applications of conversion electron emitter Tin-117m, Brazilian Archives of Biology and Technology, 50 (SPE) (2007) 49-62.

 18.V. J. Lewington, Bone-seeking radionuclides for therapy, Journal of Nuclear Medicine, 46 (1 suppl) (2005) 38S-47S.

 19.S. W. Zielhuis, J. F. W. Nijsen, J. H. Seppenwoolde, B. A. Zonnenberg, C. J. G. Bakker, W. E. Hennink, P. P. Rijk, A. D. Schip, Lanthanide bearing microparticulate systems for multi-modality imaging and targeted therapy of cancer, Current Medicinal Chemistry-Anti-Cancer Agents, 5 (3) (2005) 303-313.