Preparation and preliminary evaluation of 211At-labeled amidobisphophonates

In this paper, 3-amino-1-hydroxypropylidene-1,1-bisphosphonate(APB), a amidobisphophonate was synthesized and labeled with the alpha-emitter At-211 by an indirect method using N-succinimidyl 5-(tributylstannyl)-3-pyridinecarboxylate (SPC) as a bi-functional linker, and the conjugated amidobisphophonate (At-211-SAPC-APB) was preliminarily evaluated in vitro and in vivo by comparison with free astatide (At-211(-)) and Tc-99m-MDP. 3-amino-1-hydroxypropylidene-1,1-bisphosphonate(APB) was prepared using beta-alanine as the starting material. With SPC bi-functional linker, APB was conjugated with At-211 in a labeling yield of 80-90% with radiochemical purity of more than 99%. The conjugated amidobisphophonate (At-211-SAPC-APB) exhibited considerable stability in vitro, in that the radiochemical purity of At-211-SAPC-APB was still more than 98% in 0.1 mol/L PBS (pH 7.6) or in fetal calf serum, even stayed for 24 h at room temperature (RT). Biodistribution of At-211-SAPC-APB was investigated in NIH strain mice by I.V injection. The results showed that At-211-SAPC-APB could rapidly locate in shank, with the maximum uptake of 23.70 +/- A 2.29% I.D/g at 6 h, earlier than that of Tc-99m-MDP at 12 h, and stayed in the bone for long time. Moreover, At-211-SAPC-APB uptake in some key organs or tissues, especially in thyriod, stomach, lung and spleen, was much less than that of free astatide (At-211(-)), implying that At-211-SAPC-APB was constantly stable in vivo as well as in vitro. These results indicated that At-211-SAPC-APB will be a suitable candidate for the targeted radiotherapy of bone metastases and should be further investigated.