The comparative study of influence of MAG3 and DTPA on preparing 99Tcm-survivin ASON

Objective: To investigate the influence of different chelators on preparing 99Tcm-Survivin antisense oligonucleotide (ASON). Methods: An 18 mer single-stranded ASON sequence was synthesized and linked with a primary amine on the 5'-end. The Survivin ASON was labeled with 99Tcm by conjugating the chelator, S-acetyl-NHS-mercaptoacetyltriglycine (MAG3 ) or cyclic DTPA anhydride, respectively. The properties of 99Tcm2-MAG3-ASON and 99Tcm-DTPA-ASON, such as radiolabeling efficiency, radiochemical purity, specific activity, accumulation in hepatocellular cancer cells (HCC) and normal liver cells, were studied. Results: The radiolabeling efficiency, radiochemical purity and specific activity of 99Tcm-MAG3-ASON and 99Tcm-DTPA-ASON were (65.22 ± 6.87)% and (50.56 ± 5.45)%, 94% and 95%, 1190 and 860 kBq/μg, respectively. After incubation with normal saline at room temperature for 4 h, the radiochemical purities of both radiolabeled ASONs were more than 90%. No evidence for serum protein binding of the two labeled ASONs was observed after incubation with fresh human serum at 37 degree C in 5% CO2 for 4 h. The accumulation rate in HCCs of 99Tcm-MAG3-ASON was higher than that of 99Tcm-TPA-SON (P<0.01). The accumulation of both Survivin ASONs in HCCs was significantly higher than that in normal liver cells (P<0.01). Conclusion: The labeling methods of Survivin ASON with 99Tcm, conjugated by S-acetyl-NHS-MAG3 or cyclic DTPA anhydride, were proved to be successful. Of the two chelators, S-acetyl-NHS-MAG3 is more suitable for the radiolabeling of Survivin ASON with 99Tcm. (authors)