Astatine-211 labeling of insulin. Synthesis and preliminary evaluation in vivo and in vitro

A first attempt to label insulin, a small protein with significant affinity to tumors with the α-emitter 211At was performed by an indirect method using N-succinimidyl 5-(tributylstannyl) -3-pyridinecarboxylate (SPC) as a bi-functional linker, and the stability of the conjugated insulin (211Atinsulin) was evaluated in vitro and in vivo. SPC was synthesized by using 5-bromonicotinic acid as the starting material. With this bi-functional linker, insulin was conjugated with 211At in a labeling yield of 30 0%, with radiochemical purity of more than 98%. After 24 hours at room temperature, the radiochemical purity was still more than 95%, implying that 211At-insulin is fairly stable in vitro. Biodistribution of 211At-insulin was investigated in NIH strain mice. 211At accumulated rapidly in the liver post injection, with the maximum uptake of 4.29%I.D/g at 30 minutes, and was mainly excreted by kidney. More importantly, 211At-insulin uptake in some key organs or tissues, especially in thyriod, stomach, lung and spleen,was much less than that of free astatide (211At-). This result indicated that 211At-insulin has considerable stability in vivo as well as in vitro. (author)