170Tm-EDTMP: a potential cost-effective alternative to 89SrCl2 for bone pain palliation

Das, Tapas; Chakraborty, Sudipta; Sarma, Haladhar D.; Tandon, Pankaj; Banerjee, Sharmila; Venkatesh, Meera; Pillai, Maroor R.A.

doi:10.1016/j.nucmedbio.2009.02.002

« Previous Next »Nuclear Medicine and Biology
Volume 36, Issue 5 , Pages 561-568, July 2009

¹⁷⁰Tm-EDTMP: a potential cost-effective alternative to ⁸⁹SrCl₂ for bone pain palliation

Tapas Das
- Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai 400085, India
Sudipta Chakraborty
- Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai 400085, India
Haladhar D. Sarma
- Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400085, India
Pankaj Tandon
- Radiological Safety Division, Atomic Energy Regulatory Board, Mumbai 400094, India
Sharmila Banerjee
- Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai 400085, India
Meera Venkatesh
- Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai 400085, India
- Corresponding author. Tel.: +91 22 2559 3676; fax: +91 22 2550 5151.
Maroor R.A. Pillai
- Industrial Applications and Chemistry Section, International Atomic Energy Agency, A-1400 Vienna, Austria

Received 14 August 2008; received in revised form 15 January 2009; accepted 18 February 2009. published online 08 May 2009.

Abstract

Introduction

Metastron (⁸⁹SrCl₂) is a radiopharmaceutical currently used for bone pain palliation in several countries since the long half-life of ⁸⁹Sr (50.5 days) favors wider distribution than other radioisotopes approved for this application, which have shorter half-lives. Strontium-89 is not ideal for bone pain palliation due to its high energy β⁻ particle emission [E_β(max)=1.49 MeV] and is also difficult to produce in large quantities. A ¹⁷⁰Tm [T_1/2=128.4 days, E_β(max)=968 keV, E_γ=84 keV (3.26%)]-based radiopharmaceutical for bone pain palliation could offer significant advantages over that of ⁸⁹Sr. The present study constitutes the first report of the preparation of a ¹⁷⁰Tm-based agent, ¹⁷⁰Tm-ethylenediaminetetramethylene phosphonic acid (EDTMP), and its preliminary biological evaluation in animal models.

Methods

¹⁷⁰Tm was produced by thermal neutron bombardment on natural Tm₂O₃ target for a period of 60 days at a flux of 6×10¹³ neutrons/cm².s. ¹⁷⁰Tm-EDTMP complex was prepared at room temperature. Biodistribution and scintigraphic imaging studies with ¹⁷⁰Tm-EDTMP complex were performed in normal Wistar rats. Preliminary dosimetric estimation was made using the data to adjudge the suitability of ¹⁷⁰Tm-EDTMP for bone pain palliation.

Results

¹⁷⁰Tm was produced with a specific activity of 6.36 GBq/mg and radionuclidic purity of 100%. The ¹⁷⁰Tm-EDTMP was prepared with high radiochemical purity (>99%) and the complex exhibited satisfactory in vitro stability. Biodistribution and imaging studies showed good skeletal accumulation (50–55% of the injected activity) with insignificant uptake in any other vital organ/tissue. Activity was observed to be retained in skeleton until 60 days post-injection demonstrating that ¹⁷⁰Tm-EDTMP exhibits good bone-seeking properties with long retention. It is predicted that a dose of ∼0.5 μGy/MBq is accrued to red bone marrow and 4.3 Gy/MBq is delivered to the skeleton.

Conclusion

¹⁷⁰Tm-EDTMP shows promising biodistribution features, encouraging dosimetric values and warrants further investigation in order to develop it as a bone pain palliative radiopharmaceutical. Despite the relatively long half-life (128.4 days) of ¹⁷⁰Tm, ¹⁷⁰Tm-EDTMP could be explored as a cost-effective alternative to ⁸⁹SrCl₂.

Keywords: ¹⁷⁰Tm, EDTMP, Bone pain palliation