Radioiodination of insulin using N-succinimidyl 5-(tributylstannyl)-3-pyridine-carboxylate (SPC) as a bi-functional linker: Synthesis and biodistribution in mice</p> </p>

Summary Insulin receptors are overexpressed on a number of human tumors, leading to significant affinity of insulin to these tumors. It is appealing to receptor-targeted radiotherapy for malignant tumors if insulin is labeled with suitable radionuclide. In this paper, N-succinimidyl 5-(tributylstannyl)-3-pyridinecarboxylate (SPC), a potential bi-functional linker for radioiodination of proteins or peptides, was synthesizedby using 5-bromonicotinic acid as the starting material. Then, with this bi-functional linker, insulin was conjugated with ¹³¹I, and the tissue distribution of the labeled insulin (¹³¹I-SIPC-insulin) in normal mice was investigated. The results showed that insulin ^</span> could be conjugated with¹³¹I using SPC as the linker ^</span> in a labeling yield of40-58%, and with radiochemical purity of more than 98% after purification bySephadex?G-10. Even kept at room temperature for 72 hours, the radiochemical purity of ¹³¹I-SIPC-insulin was still more than 97%, implying that the conjugated insulin was constantly stable in vitro.Meanwhile, in order to evaluate the in vivo stability of the conjugated compounds, insulin was also labeled with ¹³¹I by a direct method using chloramine-T (Ch-T) as the electrophilic agents.Biodistribution of¹³¹I-SIPC-insulinin micesuggested that ¹³¹I could clear rapidly from the blood,mainly excreted by kidney. However, ¹³¹I uptake of mice with¹³¹I-SIPC-insulin in some key organs, especially in thyroid and stomach, were much less (150 or 30 times) than that with the direct labeled insulin (¹³¹I-insulin). Additionally, it was noted that ¹³¹I-SIPC-insulin hasmuch betterinvivo stability than¹³¹I-insulin.</p> </p>