Preparation, quality control and biodistribution assessment of ¹⁵³Sm-BPAMD as a novel agent for bone pain palliation therapy.
OBJECTIVE
Various phosphonate ligands labeled with β(-)-emitting radionuclides have shown good efficacy for bone pain palliation. In this study, a new agent for bone pain palliation has been developed.


METHODS
¹⁵³Sm-(4-{[(bis(phosphonomethyl))carbamoyl]methyl}-7,10-bis(carboxymethyl)-1,4,7,10-tetraazacyclododec-1-yl) acetic acid (¹⁵³Sm-BPAMD) complex was prepared using BPAMD ligand and ¹⁵³SmCl3. The effect of various parameters on the labeling yield of ¹⁵³Sm-BPAMD including ligand concentration, pH, temperature and reaction time were studied. Radiochemical purity of the radiolabeled complex was checked by instant thin layer chromatography (ITLC). Stability studies of the complex in the final preparation and in the presence of human serum were performed up to 48 h. Partition coefficient and hydroxyapatite (HA) binding of the complex were investigated and biodistribution studies (SPECT imaging and scarification) were performed after injection of the complex to Syrian mice up to 48 h post-injection. The biodistribution of the complex was compared with the biodistribution of the ¹⁵³Sm cation in the same type mice.


RESULTS
¹⁵³Sm-BPAMD was prepared in high radiochemical purity >98% and specific activity of 267 GBq/mmol at the optimal conditions. The complex demonstrated significant stability at room temperature and in human serum at least for 48 h. HA binding assay demonstrated that at the amount of more than 5 mg, approximately, all radiolabeled complex was bound to HA. At the pH 7.4, LogP o/w was -1.86 ± 0.02. Both SPECT and scarification showed major accumulation of the labeled compound in the bone tissue.


CONCLUSIONS
The results show that ¹⁵³Sm-BPAMD has interesting characteristics as an agent for bone pain palliation; however, further biological studies in other mammals are still needed.
Energy Engineering and Physics Department, Amir Kabir University of Technology, Tehran, Iran.
Ali
A
Rabie
Faculty of Engineering, Science and Research Branch, Islamic Azad University (IAU), Tehran, Iran.
Razieh
R
Enayati
Nuclear Science and Technology Research Institute (NSTRI), 14155-1339, Tehran, Iran. hyousefnia@aeoi.org.ir.
Hassan
H
Yousefnia
Nuclear Science and Technology Research Institute (NSTRI), 14155-1339, Tehran, Iran.
Amir Reza
AR
Jalilian
Energy Engineering and Physics Department, Amir Kabir University of Technology, Tehran, Iran.
Mojtaba
M
Shamsaei
Nuclear Science and Technology Research Institute (NSTRI), 14155-1339, Tehran, Iran.
Samaneh
S
Zolghadri
Nuclear Science and Technology Research Institute (NSTRI), 14155-1339, Tehran, Iran.
Ali
A
Bahrami-Samani
Faculty of Engineering, Science and Research Branch, Islamic Azad University (IAU), Tehran, Iran.
Mohammad
M
Hosntalab
D000818:Animals; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000528:radiation effects*; D056831:Coordination Complexes / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D004164:Diphosphonates / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D004355:Drug Stability; D017886:Durapatite / Q000378:metabolism; D006801:Humans; D051379:Mice; D063065:Organophosphonates / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D059408:Pain Management / Q000379:methods*; D010166:Palliative Care / Q000379:methods*; D011786:Quality Control; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
C000610711:153Sm-BPAMD; D056831:Coordination Complexes; D004164:Diphosphonates; D063065:Organophosphonates; D017886:Durapatite
BPAMD; Bone pain palliation; Sm-153