Journal of Nuclear Science, Engineering and Technology (JONSAT)
In cooperation with the Iranian Nuclear Society

Production, Radiolabeling and Biodistribution of 47/46Sc-DOTMP as a Radiopharmaceutical

Document Type : Research Paper

Authors

L Moghaddam B
A Bahrami-Samani
F Fathi
M Shamsaee
Abstract
Designing ideal radiopharmaceuticals for use as the bone pain palliatives requires the utilization of a moderate or low energy β-emitters with a stable carrier molecule. In this direction, cyclic polyaminophosphonic acids are known to form thermodynamically more stable and kinetically more inert complexes with lanthanides, compared to their acyclic analogs. In this study, DOTMP as the cyclic polyaminophosphonic acid and bone-seeking ligand, and 47Sc radioisotope as a low energy β-emitter with the maximum energies of 0.600MeV and 0.441MeV and the short half-life of 3.47d were considered and the therapeutic potential of the bone seeking radiopharmaceutical 47Sc-DOTMP was assessed by measuring its skeletal uptake in the animal model. Because of the limited availability of 47Sc, this study was performed  upon using 46Sc radioisotope which is chemically identical. 46Sc was produced with an activity of 2.3 (85.1 MBq) mCi by irradiation of natural 45Sc2O3 target at a thermal neutron flux of 3.5×1013 n/cm2.s in 48h at the Tehran Research Reactor (TRR). 46Sc-DOTMP was prepared in radiochemical purity of about 90% in a chelant-to-metal ratio of 60:1. The in-vitro stability of the complex was evaluated at room temperature for 48h. Then, the biodistribution studies of the complex in 5 groups of mice were carried out for 7d.

Highlights

[1] A. McEwan, Use of radionuclides for the palliation of bone metastases, In Seminars in radiation oncology Elsevier,10(2000) 103-114.

 

[2] G.M. Reisfield, E.B. Silberstein, G.R. Wilson, Radiopharmaceuticals for the palliation of painful bone metastases, Am. J. Hospice Palliative Med. 22 (2005) 41-46.

 

[3] K. Liepe, R. Runge, J. Kotzerke, The benefit of bone-seeking radiopharmaceuticals in the treatment of metastatic bone pain, J. Cancer Res. Clin. 131 (2005) 60-66.

 

[4] V.J. Lewington, Bone-seeking radionuclides for therapy. J. Nucl. Med. 46 (2005) 38S-47S.

 

[5] F.M. Paes, V. Ernani, P. Hosein, A.N. Serafini, Radiopharmaceuticals: when and how to use them to treat metastatic bone pain, J. Supportive Oncol. 9 (2011) 197-205.

 

[6] S. Banerjee, S. Chakraborty, T. Das, K. Kothari, G. Samuel, M. Venkatesh, M. Pillai, B. Mathew, H.D. Sarma, P.R. Chaudhari, 177Lu-DOTMP, 153Sm-DOTMP, 175Yb-EDTMP and 186/188Re-CTMP: Novel Agents for Bone Pain Palliation and Their Comparison with 153Sm-EDTMP, BARC NEWSLETTER. 261 (2005) 22.

 

[7] 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, Appl. Radiat. Isot. 66 (2008) 1196-1205.

 

[8] T. Das, S. Chakraborty, H.D. Sarma, S. Banerjee, 177Lu-DOTMP: a viable agent for palliative radiotherapy of painful bone metastasis, Radiochim. Acta. 96(2008) 55-61.

 

[9] S. Hassfjell, K. Ingebrigtsen, Ø.S. Bruland, Synthesis, purification and biodistribution of 205 Bi-DOTMP, visualizing bone deposition patterns with autoradiography, Nucl. Med. Biol. 28 (2001) 425-433.

 

[10] C. Müller, M. Bunka, S. Haller, U. Köster, V. Groehn, P. Bernhardt, N. Van der Meulen, A. Türler, R. Schibli, Promising Prospects for 44Sc-/47Sc-Based Theragnostics: Application of 47Sc for Radionuclide Tumor Therapy in Mice, J. Nucl. Med. 55 (2014) 1658-1664.

 

 

[11] M. Połosak, A. Piotrowska, S. Krajewski, A. Bilewicz, Stability of 47Sc-complexes with acyclic polyamino-polycarboxylate ligands, J. Radioanal. Nucl. Chem. 295 (2013) 1867-1872.

 

[12] W.T. Anderson, M. Strand, Stability, targeting, and biodistribution of scandium-46-and gallium-67-labeled monocolonal antibody in erythroleukemic mice, Cancer Res. 45 (1985) 2154-2158.

 

[13] A. Majkowska-Pilip, A. Bilewicz, Macrocyclic complexes of scandium radionuclides as precursors for diagnostic and therapeutic radiopharmaceuticals, J. Inorg. Biochem. 105 (2011) 313-320.

 

[14] M. Neves, F.C. Teixeira, I. Antunes, A. Majkowska, L. Gano, A.C. Santos, Chemical and biological evaluation of 153 Sm and 46/47 Sc complexes of indazolebisphosphonates for targeted radiotherapy, Appl. Radiat. Isot. 69 (2011) 80-84.

 

[15] L. Moghaddam-Banaem, A. Jalilian, M. Pourjavid, E. Radfar, A. Bahrami-Samani, K. Yavari, M. Mazidi, M. Ghannadi-Maragheh, Development of a radioscandium immunoconjugate for radioimmunotherapy, Radiochimica Acta International journal for chemical aspects of nuclear science and technology. 100(2012) 215-221.

 

[16] L. Moghaddam-Banaem, A.R. Jalilian, M. Pourjavid, A. Bahrami-Samani, M. Mazidi, M. Ghannadi-Maragheh, Preparation and quality control of scandium-46 bleomycin as a possible therapeutic agent, Iran. J. Nucl. Med. 20 (2012) 6.

 

[17] D. Máthé, L. Balogh, A. Polyák, R. Király, T. Márián, D. Pawlak, J.J. Zaknun, M.R. 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 (2010) 215-226.

 

[18] T. Das, S. Chakraborty, P. Unni, S. Banerjee, G. Samuel, H. Sarma, M. Venkatesh, M. Pillai, 177Lu-labeled cyclic polyaminophosphonates as potential agents for bone pain palliation, Appl. Radiat. Isot. 57 (2002) 177-184.

 

[19] B. Rosoff, H. Spencer, S. Cohn, E. Gusmano, Metabolism of scandium-46 in man, Int. J. Appl. Radiat. Isot. 16 (1965) 479-485.

Keywords

Bone-Seeking Radiopharmaceutical
46Sc-DOTMP
Radiolabeling
Biodistribution
[1] A. McEwan, Use of radionuclides for the palliation of bone metastases, In Seminars in radiation oncology Elsevier,10(2000) 103-114.
 
[2] G.M. Reisfield, E.B. Silberstein, G.R. Wilson, Radiopharmaceuticals for the palliation of painful bone metastases, Am. J. Hospice Palliative Med. 22 (2005) 41-46.
 
[3] K. Liepe, R. Runge, J. Kotzerke, The benefit of bone-seeking radiopharmaceuticals in the treatment of metastatic bone pain, J. Cancer Res. Clin. 131 (2005) 60-66.
 
[4] V.J. Lewington, Bone-seeking radionuclides for therapy. J. Nucl. Med. 46 (2005) 38S-47S.
 
[5] F.M. Paes, V. Ernani, P. Hosein, A.N. Serafini, Radiopharmaceuticals: when and how to use them to treat metastatic bone pain, J. Supportive Oncol. 9 (2011) 197-205.
 
[6] S. Banerjee, S. Chakraborty, T. Das, K. Kothari, G. Samuel, M. Venkatesh, M. Pillai, B. Mathew, H.D. Sarma, P.R. Chaudhari, 177Lu-DOTMP, 153Sm-DOTMP, 175Yb-EDTMP and 186/188Re-CTMP: Novel Agents for Bone Pain Palliation and Their Comparison with 153Sm-EDTMP, BARC NEWSLETTER. 261 (2005) 22.
 
[7] 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, Appl. Radiat. Isot. 66 (2008) 1196-1205.
 
[8] T. Das, S. Chakraborty, H.D. Sarma, S. Banerjee, 177Lu-DOTMP: a viable agent for palliative radiotherapy of painful bone metastasis, Radiochim. Acta. 96(2008) 55-61.
 
[9] S. Hassfjell, K. Ingebrigtsen, Ø.S. Bruland, Synthesis, purification and biodistribution of 205 Bi-DOTMP, visualizing bone deposition patterns with autoradiography, Nucl. Med. Biol. 28 (2001) 425-433.
 
[10] C. Müller, M. Bunka, S. Haller, U. Köster, V. Groehn, P. Bernhardt, N. Van der Meulen, A. Türler, R. Schibli, Promising Prospects for 44Sc-/47Sc-Based Theragnostics: Application of 47Sc for Radionuclide Tumor Therapy in Mice, J. Nucl. Med. 55 (2014) 1658-1664.
 
 
[11] M. Połosak, A. Piotrowska, S. Krajewski, A. Bilewicz, Stability of 47Sc-complexes with acyclic polyamino-polycarboxylate ligands, J. Radioanal. Nucl. Chem. 295 (2013) 1867-1872.
 
[12] W.T. Anderson, M. Strand, Stability, targeting, and biodistribution of scandium-46-and gallium-67-labeled monocolonal antibody in erythroleukemic mice, Cancer Res. 45 (1985) 2154-2158.
 
[13] A. Majkowska-Pilip, A. Bilewicz, Macrocyclic complexes of scandium radionuclides as precursors for diagnostic and therapeutic radiopharmaceuticals, J. Inorg. Biochem. 105 (2011) 313-320.
 
[14] M. Neves, F.C. Teixeira, I. Antunes, A. Majkowska, L. Gano, A.C. Santos, Chemical and biological evaluation of 153 Sm and 46/47 Sc complexes of indazolebisphosphonates for targeted radiotherapy, Appl. Radiat. Isot. 69 (2011) 80-84.
 
[15] L. Moghaddam-Banaem, A. Jalilian, M. Pourjavid, E. Radfar, A. Bahrami-Samani, K. Yavari, M. Mazidi, M. Ghannadi-Maragheh, Development of a radioscandium immunoconjugate for radioimmunotherapy, Radiochimica Acta International journal for chemical aspects of nuclear science and technology. 100(2012) 215-221.
 
[16] L. Moghaddam-Banaem, A.R. Jalilian, M. Pourjavid, A. Bahrami-Samani, M. Mazidi, M. Ghannadi-Maragheh, Preparation and quality control of scandium-46 bleomycin as a possible therapeutic agent, Iran. J. Nucl. Med. 20 (2012) 6.
 
[17] D. Máthé, L. Balogh, A. Polyák, R. Király, T. Márián, D. Pawlak, J.J. Zaknun, M.R. 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 (2010) 215-226.
 
[18] T. Das, S. Chakraborty, P. Unni, S. Banerjee, G. Samuel, H. Sarma, M. Venkatesh, M. Pillai, 177Lu-labeled cyclic polyaminophosphonates as potential agents for bone pain palliation, Appl. Radiat. Isot. 57 (2002) 177-184.
 
[19] B. Rosoff, H. Spencer, S. Cohn, E. Gusmano, Metabolism of scandium-46 in man, Int. J. Appl. Radiat. Isot. 16 (1965) 479-485.

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