Anti-sense oligonucleotide labeled with technetium-99m using hydrazinonictinamide derivative and N-hydroxysuccinimidyl S-acetylmercaptoacetyltriglycline: a comparison of radiochemical behaviors and biological properties.

Aim: To explore and compare the radiochemical behavior and biological property of anti-sense oligonuc-leotide (ASON) labeled with technetium-99m using N-hydroxysuccinimidyl S-acetylmercaptoacetyltriglycline (NHS-MAG(3)) and hydrazinonictinamide derivative (HYNIC).

Methods: After HYNIC and NHS-MAG(3) were synthesized, ASON was labeled with technetium-99m using HYNIC and NHS-MAG(3) as a bifunctional chelator. The in vivo and in vitro stability, binding rates of labeled compounds to serum albumen, biodistribution of (99m)Tc-MAG(3)-ASON and (99m)Tc-HYNIC-ASON in BALB/C mouse and its HT29 tumor cellular uptake were compared.

Results: The labeling efficiency and stability of (99m)Tc-MAG(3)-ASON were significantly higher than those of (99m)Tc-HYNIC-ASON (P = 0.02, and P = 0.03, respectively). (99m)Tc-MAG(3)-ASON had a significantly lower rate of binding to serum albumen than (99m)Tc-HYNIC-ASON (P < 0.05). In contrast to (99m)Tc-HYNIC-ASON, the biodistribution of (99m)Tc-MAG(3)-ASON was significantly lower in blood, heart, liver and stomach (P < 0.05), slightly lower in intestines and spleen (P > 0.05) and significantly higher in lung and kidney (P < 0.05). The HT29 tumor cellular uptake rate of (99m)Tc-MAG(3)-ASON was significantly higher than that of (99m)Tc-HYNIC-ASON (P < 0.05).

Conclusion: (99m)Tc-MAG(3)-ASON shows superior radiochemical behaviors and biological properties than (99m)Tc-HYNIC-ASON. (99m)Tc-MAG(3)-ASON is a potential radiopharmaceutical agent for in vivo application.