Labeling of Glycosylated Somatostatin With ⁹⁹Tc^m and Its Biological Evaluation

Natural somatostatin (SMS), dextran-10(Dx¹⁰) and cysteamine were used to synthesis somatostatin-dextran-cysteamine (SMS-Dx¹⁰-Cysteamine) conjugate. The in vitrosomatostatin receptor competition binding study was carried out by using ¹²⁵I-Tyr₃-Octreotide as a radioligand to measure the IC₅₀value of SMS-Dx¹⁰-Cysteamine. The SMS-Dx¹⁰-Cysteamine was radiolabeled with ⁹⁹Tc^m by using gluconate as a transchelator. The radiolabeling conditions of 99Tc^mCysteamine-Dx¹⁰-SMS and its in vitrostability were studied in detail. The biodistribution and blood halflife of ⁹⁹Tc^m-Cysteamine-Dx¹⁰-SMS were investigated in normal rats and its tumor uptake and imaging properties were evaluated in nude mice bearing human pancreatic tumor. The results show that SMS-Dx^10-Cysteamine remained high receptor binding affinity to somatostatin receptor subtype 2, and the IC₅₀value is in the same range as somatostatin. The radiolabeling efficiency of ⁹⁹Tc^m-CysteamineDx¹⁰-SMS is about 85% under optimum conditions and its radiochemical purity is more than 99% after purification. The blood halflife of ⁹⁹Tc^m-Cysteamine-Dx¹⁰-SMS in normal rats is 2.38 h post injection. The digestion and excretion is mainly through the hepatobiliary and kidney system. The ⁹⁹Tc^m-Cysteamine-Dx¹⁰-SMS is localized in pancreatic tumor and show visible tumor uptake at 6 h imaging. The results indicate that ⁹⁹Tc^m-Cysteamine-Dx¹⁰-SMS is a promising imaging agent candidate for somatostatin receptor positive tumor.