Synthesis of ~(113)In~m-p-SCN-Bz-DTPA-c-myc Antisense Oligonucleotides and Investigation of Its Inhibition Effects on the Proliferation of Vascular Smooth Muscle Cells

To investigate the effect of ~(113)In~m-pSCN-Bz-DTPA-c-myc antisense oigonucleotides(ASON) on the proliferation of vascular smooth muscle cells(VSMCs),the c-myc ASON(3'-cholestyl-TAC GGG GAG TTG CAA-C3 NH_2 5',3' end has been sulfurized) is synthesized and conjugated with the chelating agent p-SCN-Bz-DTPA,and then labeled with ~(113)In~m.The labeling yield is 45%~55%,and the radiochemical purity is higher than 90%.The stability of ~(113)In~m-DTPA-c-myc ASON in saline and in bovine serum is good,as indicated by its radiochemical purity still higher than 90% for 24 h.The hybridization ability of the radiolabeled ASON with its sense oigonucleotide(SON) counterpart(de)-monstrates its bioactivity not damaged during the synthesis.Its inhibition of the proliferation of VSMCs is dose dependent.The best inhibiton occurs at a dose of 10 μmol/L(92.5 GBq/L).The(inhibition) rates of ~(113)In~m-DTPA-c-myc ASON(radiolabeled ASON-treated group),ASON(ASON-treated group),~(113)In~mCl_3 solution(radionuclide-treated group),blank(control group),and SON(SON-treated group) are 94.92 %,69.28 %,20.55 %,15.24 % and 0 %,respectively.The inhibtion by radiolabeld ASON treatment is significantly higher(p<0.01) than that of all other treatments.These experimental results show ~(113)In~m-p-SCN-Bz-DTPA-c-myc antisense oigonucleotides can effectively inhibit the proliferation of VSMCs in vitro.