Biological Properties Evaluation of ⁹⁹Tc^m Radiolabeled a Novel Glycosylated Somatostatin

Natural somatostatin (SMS), dextran-10 (Dx10) and a new bifunctional chelator S-Acetyl-Mercaptoacetyl-glycyl-glycyl-Lysine (MAG2Lys) were used to synthesis a novel somatostatin-dextran-MAG2Lys (SMS-Dx10-MAG2Lys) conjugate and then radiolabeled with 99mTc. The in vitro somatostatin receptor competition binding study of SMS-Dx10-MAG2Lys was carried out by using rat brain cortex membranes (express somatostatin receptor type 2) and 125I-Tyr3-Octreotide as a radioligand. The biodistribution and blood half-life of 99mTc-MAG2Lys-Dx10-SMS were investigated in normal rats. The tumor uptake and imaging properties of 99mTc-MAG2Lys-Dx10-SMS were evaluated in nude mice bearing human pancreatic tumor. The SMS-Dx10-MAG2Lys shows high somatostatin receptor binding affinity, i.e. in the same IC50 value range as the reference ligand somatostatin (IC50 ~ 1.0 nmol/L). The blood half-life of 99mTc-MAG2Lys-Dx10-SMS was 2.4 h post injection in normal rats. The digestion and excretion was mainly through the hepatobiliary and kidney system. The 99mTc-MAG2Lys-Dex10-SMS was localized in pancreatic tumor and showed visible tumor uptake at 4 h imaging. The results indicate that 99mTc-MAG2Lys-Dx10-SMS is a novel promising candidate imaging agent for somatostatin receptor positive tumor.