Human organ absorbed dose estimation of 166Ho-BPAMD complex based on biodistribution data of male Syrian rats

Document Type : Original Article


Material and Nuclear Fuel Research School, Nuclear Science and Technology Research Institute, Tehran, Iran


Introduction: Recently, 166Ho-BPAMD was introduced as a suitable agent for bone marrow ablation. The aim of this study was to estimate the absorbed dose of this novel agent in the human organs which is necessary before the clinical application.
Methods: 166Ho was produced by direct irradiation of 165Ho in the research reactor. 250 µg of BPAMD was added to the vial containing 111 MBq of 166Ho and the pH of the reaction mixture was adjusted to 6 while it was incubated for 45 min at 90-100°C. The strong cation exchanger was applied to improve the radiochemical purity checked by ITLC method. 166Ho-BPAMD was injected to male Syrian rats and the uptake in different organs was assessed. The absorbed dose in human organs was estimated following the mass extrapolation and according to RADAR method.
Results:166Ho-BPAMD was prepared with the radiochemical purity of higher than 96%. After injection to male Syrian rats, the most of the activity was observed in the bone tissues. Bone surface and bone marrow received the highest amounts of the absorbed dose with the value of 0.916 and 0.647 mGy/MBq, respectively.
Conclusion: Bone marrow to the bone tissue and total body absorbed dose ratio for 166Ho-BPAMD was comparable to the other bone seeking radiopharmaceuticals. 166Ho-BPAMDdelivers safe and reasonably appropriate dose to the human organs and can be considered as a novel bone marrow ablative agent.


Main Subjects

  1. Bayouth JE, Macey DJ, Kasi LP, Garlich JR, McMillan K, Dimopoulos MA, Champlin RE. Pharmacokinetics, dosimetry and toxicity of holmium-166-DOTMP for bone marrow ablation in multiple myeloma. J Nucl Med. 1995 May;36(5):730-7.
  2. Knapp FF, Dash A. Radiopharmaceuticals for Therapy. New Delhi: Springer; 2016.
  3. Salek N, Vosoghi S, Arani SS, Samani AB, Mehrabi M, Maraghe MG. Preparation and dosimetry evaluation of a carrier- free 90Y labeled DOTMP as a promising agent for bone marrow ablation. Curr Radiopharm. 2018;11(2):116-122.
  4. Macfarlane DJ, Durrant S, Bartlett ML, Allison R, Morton AJ. 153Sm EDTMP for bone marrow ablation prior to stem cell transplantation for haematological malignancies. Nucl Med Commun. 2002;23(11):1099-1106.
  5. Vaez-Tehrani M, Zolghadri S, Yousefnia H, Afarideh H.  Estimation of human absorbed dose for 166Ho-PAM: comparison with 166Ho-DOTMP and 166Ho-TTHMP. Br J Radiol. 2016; 89(1066): 20160153.
  6. Rajendran JG, Eary JF, Bensinger W, Durack LD, Vernon C, Fritzberg A. High-Dose 166Ho-DOTMP in myeloablative treatment of multiple myeloma: pharmacokinetics, biodistribution, and absorbed dose estimation. J Nucl Med. 2002;43:1383–1390.
  7. Drake MT,  Clarke BL, Khosla S.  Bisphosphonates: Mechanism of action and role in clinical practice.  Mayo Clin Proc. 2008 Sep; 83(9): 1032–1045. 
  8. Correa-González L, Arteaga de Murphy C, Pichardo-Romero P, Pedraza-López M, Moreno-García C, Correa-Hernández L. (153)Sm-EDTMP for pain relief of bone metastases from prostate and breast cancer and other malignancies. Arch Med Res. 2014;45(4):301-8.
  9. Anderson P, Nuñez R. Samarium lexidronam (153Sm-EDTMP): skeletal radiation for osteoblastic bone metastases and osteosarcoma. Expert Rev Anticancer Ther. 2007;7(11):1517-27.
  10. Fellner M, Biesalski B, Bausbacher N, Kubícek V, Hermann P, Rösch F, Thews O. (68)Ga-BPAMD: PET-imaging of bone metastases with a generator based positron emitter. Nucl Med Biol. 2012;39(7):993-9.
  11. Yousefnia H, Zolghadri S, Sadeghi HR, Naderi M, Jalilian AR, Shanehsazzadeh S. Preparation and biological assessment of 177Lu-BPAMD as a high potential agent for bone pain palliation therapy: comparison with 177Lu-EDTMP. J Radioanal Nucl Chem. 2016;307(2):1243-51.
  12. Yousefnia H, Zolghadri S. Estimated human absorbed dose of a new 153Sm bone seeking agent based on biodistribution data in mice: Comparison with 153Sm-EDTMP. Phys Med. 2015;31(7):714–9.
  13. Yousefnia H, Amraei N, Hosntalab M, Zolghadri S, Bahrami-Samani A. Preparation and biological evaluation of 166Ho-BPAMD as a potential therapeutic bone-seeking agent. J Radioanal Nucl Chem. 2015;304(3):1258-91.
  14. Stabin MG, Tagesson M, Thomas SR, Ljungberg M, Strand SE. Radiation dosimetry in nuclear medicine. Appl Radiat Isot. 1996;50:73-87.
  15. Vigna L, Matheoud R, Ridone S, Arginelli D, Della Monica P, Rudoni M, Inglese E, Brambilla M. Characterization of the [153Sm]Sm-EDTMP pharmacokinetics and Estimation of radiation absorbed dose on an individual Basis. Phys Med. 2011;27:144-152.
  16. Kesner AL,  Hsueh WA, Czernin J, Padgett H, Phelps ME, Silverman DH. Radiation dose estimates for [18F]5-fluorouracil derived from PET-based and tissue-based methods in rats. Mol Imaging Biol. 2008;10:341-8.
  17. ICRP Publication 62. Radiological protection in biomedical research. Ann ICRP. 1993;22(3).
  18. Stabin MG, Siegel JA. Physical models and dose factors for use in internal dose assessment. Health Phys. 2003;85:294-310.
  19. Biological Council. Guidelines on the use of living animals in scientific investigations. UK: Biological Council; 1987.
  20. IAEA-TECDOC-1340. Manual for reactor produced radioisotopes. Austria: IAEA; 2003.
  21. Sparks RB, Aydogan B. Comparison of the effectiveness of some common animal data scaling techniques in estimating human radiation dose, Sixth International Radiopharmaceutical Dosimetry Symposium. Oak Ridge, TN: Oak Ridge Associated Universities, 1996;705-16.
  22. Yousefnia H, Zolghadri S, Jalilian AR. Absorbed dose assessment of 177Lu-zoledronate and 177Lu-EDTMP for human based on biodistribution data in rats. J Med Phys. 2015;40(2): 102–108.
  23. 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;46:1023-7.
  24. Kesner AL, Hsueh W-A, Czernin J, Padgett H, Phelps ME, Silverman DH. Radiation dose estimates for [18F] 5-fluorouracil derived from PET-based and tissue-based methods in rats. Mol Imaging Biol. 2008;10(6):341-8.