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World J Gastroenterol. Apr 14, 2008; 14(14): 2235-2240
Published online Apr 14, 2008. doi: 10.3748/wjg.14.2235
Anti-sense oligonucleotide labeled with technetium-99m using hydrazinonictinamide derivative and N-hydroxysuccinimidyl S-acetylmercaptoacetyltriglycline: A comparison of radiochemical behaviors and biological properties
Yun-Chun Li, Tian-Zhi Tan, Jian-Guo Zheng, Chun Zhang
Yun-Chun Li, Tian-Zhi Tan, Jian-Guo Zheng, Chun Zhang, Department of Nuclear Medicine, West China Hospital, Sichuan University, 37 Guoxue Alley, Chengdu 610041, Sichuan Province, China
Author contributions: Li YC, Tan TZ, Zheng JG, Zhang C contributed equally to this work.
Correspondence to: Tian-Zhi Tan, Professor, Department of Nuclear Medicine, West China Hospital, Sichuan University, 37 Guoxue Alley, Chengdu 610041, Sichuan Province, China. ttz@mcw-cums.com
Telephone: +86-28-81812589
Fax: +86-28-85422697
Received: November 12, 2007
Revised: January 30, 2008
Published online: April 14, 2008
Abstract

AIM: To explore and compare the radiochemical behavior and biological property of anti-sense oligonucleotide (ASON) labeled with technetium-99m using N-hydroxysuccinimidyl S-acetylmercaptoacetyltriglycline (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.

Keywords: Anti-sense oligonucleotide; Radiolabeling; Technetium-99m; N-hydroxysuccinimidyl S-acetylmercaptoacetyltriglycline; Hydrazinonictionamide derivative