Animal-based radiation absorbed dose evaluation of holmium-166 labeled hydroxyapatite particulates in liver malignancies

Document Type : Original Article

Authors

1 Radiation Applications Research School, Nuclear Science and Technology Research Institute, Tehran, Iran

2 Nuclear Fuel Cycle Research School, Nuclear Science and Technology Research Institute, Tehran, Iran

Abstract

Objective(s): Liver malignancies are among the most prevalent causes of cancer-related deaths worldwide. Intra-arterial administration of particulates labeled with beta-emitting radionuclides is one of the non-surgical promising modalities for the treatment of liver cancer.
Methods: In this work, the radiation absorbed dose of 166Ho-hydroxyapatite (166Ho-HA) radiopharmaceutical was estimated for adult men based on biodistribution data in normal Wistar rats. The MIRD dose calculation method and the Sparks and Aydogan methodology were applied.
Results: The results show that more than 84% of the absorbed dose is localized in liver tissue (7.35 mGy MBq-1). Also, radiation absorbed doses of 166Ho-HA for red bone marrow, osteogenic cells, and spleen tissues were estimated to be about 0.18, 0.38, and 0.24 mGy MBq-1, respectively. The maximum administrated activity was obtained at 87.5 MBq kg-1 of body weight with an effective dose of 0.39 mSv MBq-1. The maximum tolerable dose (MTD) for liver tissue was 6.13 GBq (165.56 mCi).
Conclusion: This study indicated that 166Ho-HA can provide an impressive dose for liver cancer malignancies with an insignificant dose to healthy tissues.

Keywords

Main Subjects


  1. Nijsen JFW, Schip AD van het, Hennink WE, Rook DW, Rijk PP van, et al. Advances in nuclear oncology: Microspheres for internal radionuclide therapy of liver tumors. Curr Med Chem. 2002; 9(1):73-82.
  2. Vente MAD, Hobbelink MGG, Schip AD van het, Zonnenberg BA, Nijsen JFW. Radionuclide liver cancer therapy: From concept to current clinical status. Anti-Cancer Agents Med Chem. 2007; 7(4):441-459.
  3. Häfeli UO, Casillas S, Dietz DW, Pauer GJ, Rybicki LA, Conzone SD, et al. Hepatic tumor radioembolization in a rat model using radioactive rhenium (186Re/188Re) glass microspheres. Int J Radiat Oncol Biol Phys. 1999; 44(1):189-199.
  4. Farmer DG, Basuttil RW. The role of multimodal therapy in treatment of hepatocellular carcinoma. Cancer. 1994; 73(11):2669-2670.
  5. Nijsen F, Rook D, Brandt C, Dullens H, Zonnenberg B, Klerk J de, et al. Targeting of liver tumor in rats by selective delivery of holmium-166 loaded microspheres: A biodistribution study. Eur J Nucl Med. 2001; 28(6):743-749.
  6. Nijsen JFW, Jonnenberg BA, Woittiez JR, Rook DW, Swildens-van Woudenberg IA, Rijk PP van, et al. Holmium-166 polylactic acid microspheres applicable for intra-arterial radionuclide therapy of hepatic malignancies: Effects of preparation and neutron activation techniques. Eur J Nucl Med. 1999; 26(7):699-704.
  7. Ehrhardt GJ, Day DE. Therapeutic use of Y-90 microsphere. Int J Radiat Appl Instrum Part B Nucl Med Biol. 1987; 14(3):233-242.
  8. Lin M, Shon IH, Wilson R, D'Amours SK, Schlaphoff G, Lin P. Treatment response in liver metastases following 90Y SIR-spheres: An evaluation with PET. Hepato-Gastroenterol. 2007; 54(75):910-912.
  9. Mumper RJ, Ryo UY, Jay M. Neutron activated holmium-166-poly (L-lactic acid) microspheres: A potential agent for the internal radiation therapy of hepatic J Nucl Med. 1991; 32(11):2139-2143.
  10. Das T, Chakraborty S, Sarma HD, Venkatesh M, Banerjee S. 166Ho-Labeled hydroxyapatite particles: A possible agent for liver cancer therapy. Cancer Biother Radiopharm. 2009; 24(1):7-13.
  11. Bagheri R, Afarideh H, Ghannadi-Maragheh M, Shirmardi SP, Bahrami-Samani A. Study of bone surface absorbed dose in the treatment of bone metastases via selected radiopharmaceuticals: using MCNP4C code and available experimental data. Cancer Biother Radiopharm. 2015; 30(4):174-181.
  12. Bahrami-Samani A, Bagheri R, Jalilian AR, Shirvani-Arani S, Ghannadi-Maragheh, M, Shamsaee M. Production, quality control and pharmacokinetic studies of 166Ho-EDTMP for therapeutic applications. Sci Pharm. 2010; 78(3):423-433.
  13. Bagheri R, Jalilian AR, Bahrami-Samani A, Mazidi M, Ghannadi-Maragheh M. Production of Holmium-166 DOTMP: a promising agent for bone marrow ablation in hematologic malignancies. Iran J Nucl Med. 2011; 19(1):12-20.
  14. Unni PR, Chaudhari PR, Venkatesh M, Ramamoorthy N, Pillai MRA. Preparation and bioevaluation of 166Ho labeled hydroxyapatite (HA) particles for radio-synovectomy. Nucl Med Biol. 2002; 29(2):199-209.
  15. Chakraborty S, Das T, Banerjee S, Subramanian S, Sarma H Dev, Venkatesh M. 175Yb-labelled hydroxyapatite: A potential agent for use in radiation synovectomy of small joints. Nucl Med Biol. 2006; 33(4):585-591.
  16. Belanger MJ, Krause SM, Ryan C, Sanabria-Bohorquez S, Li W, Hamill TG, et al. Biodistribution and radiation dosimetry of 18F-PEB in nonhuman primates. Nucl Med Commun. 2008; 29(10):915-919.
  17. Bagheri R. 177Lu-EDTMP radiation absorbed dose evaluation in man based on biodistribution data in Wistar rats. Nucl Eng Technol. 2023; 55(1):254-260.
  18. Bagheri R, Bahrami-Samani A, Ghannadi-Maragheh M. Estimation of radiation absorbed dose in man from 166Ho-EDTMP based on biodistribution data in Wistar rats. Radiat. Phys. Chem. 2021; 187 (109560):1-6.
  19. Bolch WE, Eckerman KF, Sgouros G, Thomas SR. MIRD pamphlet No. 21: a generalized schema for radiopharmaceutical dosimetry standardization of nomenclature. J Nucl Med. 2009; 50(3):477-484.
  20. Sparks RB, Aydogan B. Comparison of the effectiveness of some common animal data scaling techniques in estimating human radiation dose, in: Proceedings of the Sixth International Radiopharmaceutical Dosimetry Symposium, Oak Ridge Associated Universities, Oak Ridge, TN, 1996; 705-716.
  21. Stabin MG, Sparks RB, Crowe E. OLINDA/EXM: the Second-generation personal computer software for internal dose assessment in nuclear medicine. J Nucl Med. 2005; 46(6):1023-1027.
  22. ICRP, ICRP Publication 103, the 2007 Recommendations of the International Commission on Radiological Protection, volume 37, Elsevier, 2007.
  23. Milano MT, Constine LS, Okunieff P. Normal tissue tolerance dose metrics for radiation therapy of major organs. Semin Radiat Oncol. 2007; 17(2):131-140.
  24. Breitz HB, Wendt III RE, Stabin MS, Shen S, Erwin WD, Rajendran JG, et al. 166Ho-DOTMP radiation-absorbed dose estimation for skeletal targeted radiotherapy. J Nucl Med. 2006; 47(3):534-542.
  25. Emami B. Tolerance of normal tissue to therapeutic radiation. Rep Radiother Oncol. 2013; 1(1):35-48.
  26. Sharma S, Singh B, Koul A, Mittal BR. Comparative therapeutic efficacy of 153Sm-EDTMP and 177Lu-EDTMP for bone pain palliation in patients with skeletal metastases: patients' pain score analysis and personalized dosimetry. Front Med. 2017; 4(46):1-9.
  27. Louw WKA, Domehl C, Rensburg AJ van, Hugo N, Alberts AS, Forsyth OE, et al. Evaluation of samarium-153 and holmium-166-EDTMP in the normal baboon model. Nucl Med Biol. 1996; 23(8):935-940.
  28. Reisfield GM, Silberstein EB, Wilson GR. Radiopharmaceuticals for the palliation of painful bone metastases. Am J Hosp Palliat Care. 2005; 22(1):41-46.
  29. Manafi-Farid R, Masoumi F, Divband G, Saidi B, Ataeinia B, Hertel F, et al. Targeted palliative radionuclide therapy for metastatic bone pain. J Clin Med. 2020; 9(8):1-2.
  30. ICRP, ICRP Publication 89, Basic Anatomical and Physiological Data for Use in Radiological Protection: Reference Values, Pergamon Press, New York, 2002.