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


CONCLUSIONS
(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.
Li
Yun-Chun
YC
Department of Nuclear Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China.
Tan
Tian-Zhi
TZ
Zheng
Jian-Guo
JG
Zhang
Chun
C
D000818:Animals; D045744:Cell Line, Tumor; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008956:Models, Chemical; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology*; D016376:Oligonucleotides, Antisense / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding; D011817:Rabbits; D011854:Radiochemistry / Q000379:methods; D019275:Radiopharmaceuticals / Q000494:pharmacology; D013388:Succinimides / Q000494:pharmacology*; D013667:Technetium / Q000494:pharmacology*; D014018:Tissue Distribution
C530515:N-hydroxysuccinimidyl S-acetylmercaptoacetyltriglycline; D016376:Oligonucleotides, Antisense; D019275:Radiopharmaceuticals; D013388:Succinimides; C530514:hydrazinonictinamide; D009536:Niacinamide; D013667:Technetium; D005998:Glycine