Radiolabeling and evaluation of two 177Lu-labeled bis-phosphonates

Document Type: Original Article


1 Department of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

2 Radiopharmacy Research Group, Radiation Application Research School, Nuclear Science and Technology Research Institute, Tehran, Iran


Introduction: Bone pain palliation therapy is a mandate in handling end-stage cancer patients. The development of new ligands with higher stability, better pharmacokinetics and lower unwanted tissue uptakes (liver and GI) is still ongoing. Methods: In this work Lu-177 labeled (3-amino-1-hydroxypropane-1,1-di-yl)-bis-(phosphonate) (177Lu-pamidronate; 177Lu-PAM ), and (3-amino-1-hydroxybutane-1,1-di-yl)-bis-(phosphonate) (177Lu-alendronate; 177Lu-ALN)  complexes were prepared successfully using related ligands and 177LuCl3 at 25ºC & 60ºC at various ligand:metal ratios for 60-360 min. Lu-177 chloride was obtained by thermal neutron irradiation (4 × 1013 of natural Lu2O3 samples. Radiochemical purities of 177Lu- complexes were checked by ITLC and HPLC. Stability studies of final preparation in the presence of human serum were evaluated along with protein binding studies as well as hydroxyapatite (HA) binding test. The biodistribution of 177Lu-complexes and 177LuCl3 in mice were determined for 7 d. Results: The complexes were obtained in high radiochemical purity ITLC (>97%) and HPLC (>99.9%). Satisfactory stability in presence of human serum and final formulations were obtained (»90% in 48 h).HA binding assay demonstrated >98% binding from 5-20 mg. The complex protein binding was about 50-58%. Conclusion: Biodistribution of both complexes demonstrated low bone uptake ratios at all time intervals, for far inferior to 177Lu-EDTMP.


Main Subjects

Serafini AN. Therapy of metastatic bone pain. J Nucl Med. 2001 Jun;42(6):895-906.

Campa JA 3rd, Payne R. The management of intractable bone pain: a clinician's perspective. Semin Nucl Med. 1992 Jan;22(1):3-10.

Eary JF, Collins C, Stabin M, Vernon C, Petersdorf S, Baker M, Hartnett S, Ferency S, Addison SJ, Appelbaum F, Gordon EE. Samarium-153-EDTMP biodistribution and dosimetry estimation. J Nucl Med. 1993 Jul;34(7):1031-6.

Yousefnia H, Jalilian AR, Zolghadri S, Ghannadi-Maragheh M. Production, quality control, biodistribution assessment and preliminary dose evaluation of (177)Lu-PDTMP as a possible bone palliative agent. Nucl Med Commun. 2014 Jan;35(1):99-107.

Bahrami-Samani A, Anvari A, Jalilian AR, Shirvani-Arani S, Yousefnia H, Aghamiri MR, Ghannadi-Maragheh M. Production, Quality Control and Pharmacokinetic Studies of (177)Lu-EDTMP for Human Bone Pain Palliation Therapy Trials. Iran J Pharm Res. 2012 Winter;11(1):137-44.

Alavi MS, Omidvari S, Mehdizadeh A, Gheisari F. Metastatic bone pain palliation using 177Lu- EDTMP [abstract]. Iran J Nucl Med. 2012;20(Suppl 1):50.

Nikzad M, Jalilian AR, Shirvani-Arani S, Bahrami-Samani A, Golchoubian H. Production, quality control and pharmacokinetic studies of 177Lu–zoledronate for bone pain palliation therapy. J Radioanal Nucl Chem. 2013;298(2):1273-1281.

Zolghadri S, Jalilian AR, Naseri Z, Yousefnia H, Bahrami-Samani A, Ghannadi-Maragheh M, Afarideh H. Production, quality control and biological evaluation of (166)Ho-PDTMP as a possible bone palliation agent. Iran J Basic Med Sci. 2013 May;16(5):719-25.

Zolghadri S, Jalilian AR, Yousefnia H, Bahrami-Samani A, Fazaeli Y, Pouladi M, Ghannadi-Maragheh M, Afarideh H. The synthesis, radiolabeling and first biological evaluation of a new 166Ho-complex for radiotherapy of bone metastases. Radiochimica Acta. 2013;101(7):445-51.

International Atomic Energy Agency. Manual for reactor produced radioisotopes. Vienna: IAEA; 2003. p.121-23.

EANM Radiopharmacy Committee, Guidelines on current good Radiopharmacy Practice (cGRPP) in the Preparation of Radiopharmaceuticals. cGRPP-guidelines, version 2, March 2007.

Dar UK, Khan IU, Javed M, Ahmad F, Ali M, Hyder SW. Preparation and biodistribution in mice of a new radiopharmaceutical-technetium-99m labeled methotrexate, as a tumor diagnostic agent. Hell J Nucl Med. 2012 May-Aug;15(2):120-4.

Neves M, Gano L, Pereira N, Costa MC, Costa MR, Chandia M, Rosado M, Fausto R. Synthesis, characterization and biodistribution of bisphosphonates Sm-153 complexes: correlation with molecular modeling interaction studies. Nucl Med Biol. 2002 Apr;29(3):329-38.

Du XL, Zhang TL, Yuan L, Zhao YY, Li RC, Wang K, Yan SC, Zhang L, Sun H, Qian ZM. Complexation of ytterbium to human transferrin and its uptake by K562 cells. Eur J Biochem. 2002 Dec;269(24):6082-90.