摘要
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-acetylmercaptoacetyltriglycl ine (NHS-MAG3) and hydrazinonictinamide derivative (HYNIC). METHODS:After HYNIC and NHS-MAG3 were synthesized, ASON was labeled with technetium-99m using HYNIC and NHS-MAG3 as a bifunctional chelator. The in vivo and in vitro stability, binding rates of labeled compounds to serum albumen, biodistribution of 99mTc-MAG3-ASON and 99mTc-HYNIC-ASON in BALB/C mouse and its HT29 tumor cellular uptake were compared. RESULTS:The labeling efficiency and stability of 99mTc-MAG3-ASON were significantly higher than those of 99mTc-HYNIC-ASON (P = 0.02, and P = 0.03, respectively). 99mTc-MAG3-ASON had a significantly lower rate of binding to serum albumen than 99mTc-HYNIC-ASON (P < 0.05). In contrast to 99mTc-HYNIC-ASON, the biodistribution of 99mTc-MAG3-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 99mTc-MAG3-ASON was significantly higher than that of 99mTc-HYNIC-ASON (P < 0.05). CONCLUSION:99mTc-MAG3-ASON shows superior radiochemical behaviors and biological properties than 99mTc-HYNIC-ASON. 99mTc-MAG3-ASON is a potential radiopharmaceutical agent for in vivo application.
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-acetylmercaptoacetyltriglycl ine （NHS-MAG3） and hydrazinonictinamide derivative （HYNIC）. METHODS：After HYNIC and NHS-MAG3 were synthesized, ASON was labeled with technetium-99m using HYNIC and NHS-MAG3 as a bifunctional chelator. The in vivo and in vitro stability, binding rates of labeled compounds to serum albumen, biodistribution of ^99mTc-MAG3-ASON and ^99mTc-HYNIC-ASON in BALB/C mouse and its HT29 tumor cellular uptake were compared. RESULTS：The labeling efficiency and stability of ^99mTc-MAG3-ASON were significantly higher than those of ^99mTc-HYNIC-ASON （P = 0.02, and P = 0.03, respectively）. ^99mTc-MAG3-ASON had a significantly lower rate of binding to serum albumen than ^99mTc-HYNIC-ASON （P 〈 0.05）. In contrast to ^99mTc-HYNIC-ASON, the biodistribution of ^99mTc-MAG3-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 ^99mTc-MAG3-ASON was significantly higher than that of ^99mTc-HYNIC-ASON （P 〈 0.05）. CONCLUSION：^99mTc-MAG3-ASON shows superior radiochemical behaviors and biological properties than ^99mTc-HYNIC-ASON. ^99mTc-MAG3-ASON is a potential radiopharmaceutical agent for in vivo application.
基金
The National Natural Science Foundation of China, No. 39870200
