Objective: Thulium-170 [T_1/2 = 128.4 days, E_β(max) = 968 keV, and Eγ = 84 keV (3.26%)] could be considered an easily producible and cost-effective alternative to 89Sr for the preparation of radiopharmaceuticals for palliation of bone pain arising due to skeletal metastases. Multidentate aminomethylene polyphosphonic acids have already been proven to be effective as carrier moieties for developing radiolabeled bone pain palliation agents using lanthanide radionuclides. Therefore, an attempt was made to evaluate the potential of a series of ¹⁷⁰Tmlabeled acyclic (diethylenetriaminepentamethylene phosphonic acid and triethylenetetraminehexamethylene phosphonic acid) and cyclic polyaminopolyphosphonic acids (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene phosphonic acid [DOTMP] and 1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetramethylene phosphonic acid [CTMP]) toward their use as alternative bone pain palliation agents.

Experimental: Thulium-170 was produced by irradiating the natural Tm₂O₃ target at a thermal neutron flux of 7 X10¹³ n.cm^-2.s^-1 for a period of 60 days. All the phosphonic acid ligands were synthesized and characterized in-house. The protocols for radiolabeling the phosphonic acids with ¹⁷⁰Tm were standardized. Biological evaluation of the ¹⁷⁰Tm-labeled phosphonic acids were carried out in normalWistar rats by biodistribution as well as by scintigraphic studies.

Results: Thulium-170 was produced with adequate specific activity (173 Ci/g, 6.41 TBq/g) and high radionuclidic purity (99.62%). All the ¹⁷⁰Tm-labeled phosphonic acids, except ¹⁷⁰Tm-CTMP, were prepared with very high radiochemical purity ( >98%) under optimized reaction conditions and exhibited high stability. All the agents showed selective skeletal accumulation with insignificant uptake in other vital organs/tissues and major clearance through renal pathway. These findings were also substantiated by scintigraphic studies.

Conclusions: Although all the 170Tm-labeled phosphonic acids showed significant and selective skeletal accumulation, radiochemical studies indicate that 170Tm-DOTMP is the best choice for carrying out further evaluation toward its use for clinical applications.