Production, Quality Control and Biological Evaluation of 166Ho-PDTMP as a Possible Bone Palliation Agent

Document Type : Original Article

Authors

1 Radiopharmaceutical Research & Development Laboratory (RRDL), Nuclear Science and Technology Research Institute (NSTRI), Tehran, Iran 2 Faculty of Energy Engineering and Physics, Amirkabir University of Technology, Tehran, Iran

2 Radiopharmaceutical Research & Development Laboratory (RRDL), Nuclear Science and Technology Research Institute (NSTRI), Tehran, Iran 2 Faculty

3 Radiopharmaceutical Research & Development Laboratory (RRDL), Nuclear Science and Technology Research Institute (NSTRI), Tehran, Iran

4 Faculty of Energy Engineering and Physics, Amirkabir University of Technology, Tehran, Iran

Abstract

Objective(s):In this study, 166Ho-1,2-propylene di-amino tetra(methy1enephosphonicAcid) (166Ho-PDTMP) complex  was prepared as a bone palliation agent.
Materials and Methods:The complex was successfully prepared using an in-house synthesized EDTMP ligand and 166HoCl3. Ho-166 chloride was obtained by thermal neutron irradiation (1 × 1013 n.cm-2.s-1) of natural Ho(NO3)3 samples  followed by radiolabeling and stability studies. Biodistribution in wild type rats was also peformed.
Results: The complex was prepared with thespecific activity of 278 GBq/mg and high radiochemical purity (>99%, checked by ITLC). 166Ho-PDTMP complex was stabilized in the final preparation and in the presence of human serum (>90%) up to 72 hr. The biodistribution of 166Ho-PDTMP in wild-type rats demonstrated significant bone uptake was up to 48 hr compared to 166HoCl3.
Conclusion: The produced 166Ho-PDTMP properties suggest a possible new bone palliative therapeutic to overcome the metastatic bone pains.
 

Keywords

References

1. Serafini AN. Therapy of metastatic bone pain. J Nucl Med 2001; 42:895-906.
2. Bayouth JE, Macey DJ, Kasi LP, Fossella FV. Dosimetry and toxicity of Samarium-153-EDTMP administered for bone pain to skeletal metastases. J Nucl Med 1994; 35:63-69.
3. Campa JA, Rayne R. The management of intractable bone pain: a clinician’s perspective. Semin Nucl Med 1992; 22: 3-10.
4. Eary JF, Collin C, Stabin M, Vernon C, Petersdorf S, Baker M, et al. Samarium-153-EDTMP biodistribution and dosimetry estimation. J Nucl Med 1993; 34:1031-1036.
5. Holmes A. 153Sm-EDTMP: a potential therapy for bone cancer. Semin Nucl Med 1992; 22: 41-45.
6. Serafini AN, Houston SJ, Resche I, Quick DP, Grund FM, Ell PJ, et al. Palliation of pain associated with metastatic bone cancer using samarium-153 lexidronam: a double-blind pacebo-controlled clinical trial. J Clin Oncol 1998; 16:574-1581.
7. Máthé D, Balogh L, Polyák A, Király R, Márián T, Pawlak D, et al. Multispecies animal investigation on biodistribution, pharmacokinetics and toxicity of 177Lu-EDTMP, a potential bone pain palliation agent. Nucl Med Biol 2010; 37:215-226.
8. Breitz HB, Wendt III RE, Stabin MS, Shen S, Erwin WD, Rajendrann JG, et al. 166Ho-DOTMP radiation-absorbed dose estimation for skeletal targeted radiotherapy. J Nucl Med 2006; 47:534–542
9. Bahrami-Samani A, Ghannadi-Maragheh M, Jalilian AR, Meftahi M, Shirvani-Arani S, Moradkhani S. Production, quality control and biological evaluation of 153Sm-EDTMP in wild-type rodents. Iran J Nucl Med 2009; 17:12-19.
10. Ouadi A, Loussouarn A, Morandeau L, Remaud P, Faivre-Chauvet A, Webb J, et al. Influence of trans-1,2-diaminocyclohexane structure and mixed carboxylic/phosphonic group combinations on samarium-153 chelation capacity and stability. Eur J Med Chem 2004; 39:467–472.
11. Majali MA, Mathakar AR, Shimpi HH, Banerjeea S, Samuel G. Studies on the preparation and stability of samarium-153 propylene diamine tetramethylene phosphonate (PDTMP) complex as a bone seeker. Appl Radiat Iso 2000; 53:987-991.
12. Zeevaart JR, Jarvis NV, Werner KA, Jackson GE. Metal-ion speciation in blood plasma incorporating the tetraphosphonate, N,N-dimethylenephosphonate-1-hydroxy-4-aminopropilydenediphosphonate (APDDMP), in therapeutic radiopharmaceuticals. J Inorg Biochem 2001; 83:57–65.
13. Bahrami-Samani A, Bagheri R, Jalilian AR, Shirvani-Arani S, Ghannadi-Maragheh M, Shamsaee M. Production, quality control and pharmacokinetic studies of Ho-EDTMP for therapeutic applications. Sci Pharm 2010; 78:423-433.
14.  Chakraborthy S, Das T, Unni PR, Sarma HD, Samuel G, Banerjee S, et al. 177Lu-labelled polyaminophosphonates as potential agents for bone pain palliation. Nucl Med Commun 2002; 23:67-74.
15. Manual for reactor produced radioisotopes, IAEA, 2003, IAEA-TECDOC-1340,ISBN 92-0-101103-2, ISSN 1011-4289, © IAEA, 2003, pp.71, Printed by the IAEA in Austria, January 2003.
16. Moedritzer K, Irani RR. Direct synthesis of α- aminomethyl phosphonic acid: mannich type reactions with o- phosphorus acid. J Org Chem 1996; 31:1603-1607.
 
 
 

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