Synthesis and Characterization of Nitroimidazole Derivatives for 68Ga-Labeling and Testing in Tumor Xenografted Mice

被引：54

作者：

Hoigebazar, Lathika ^{[1
,2
]}

Jeong, Jae Min ^{[1
,2
]}

Choi, Soo Young ^{[3
,4
]}

Choi, Jae Yeon ^{[1
,2
]}

Shetty, Dinesh ^{[1
,2
]}

Lee, Yun-Sang ^{[1
,2
]}

Lee, Dong Soo ^{[1
,2
]}

Chung, June-Key ^{[1
,2
]}

Lee, Myung Chul ^{[1
,2
]}

Chung, Young Keun ^{[3
,4
]}

机构：

[1] Seoul Natl Univ, Coll Med, Dept Nucl Med, Inst Radiat Med, Seoul 110744, South Korea

[2] Seoul Natl Univ, Coll Med, Canc Res Inst, Seoul 110744, South Korea

[3] Seoul Natl Univ, Dept Chem, Seoul, South Korea

[4] Seoul Natl Univ, Intelligent Text Syst Res Ctr, Seoul, South Korea

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2010年 / 53卷 / 17期

关键词：

POSITRON-EMISSION-TOMOGRAPHY; IN-VIVO; GALLIUM(III) COMPLEX; CRYSTAL-STRUCTURE; HYPOXIA MARKERS; IMAGING HYPOXIA; PET TRACER; HEAD; BIODISTRIBUTION; AGENT;

D O I：

10.1021/jm100545a

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Radiolabeled nitroimidazole (NI) derivatives have been used for imaging hypoxic tissues. We synthesized NI derivatives conjugated with bifunctional chelating agents such as 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) and isothiocyanatobenzyl-NOTA (SCN-NOTA) via ethyleneamine bridge by formation of amide and thiourea bond, respectively. We proved that amide oxygen of Ga-NOTA-NI contributes to the formation of metal complex by X-ray crystallography. We labeled them with Ga-68 and found that both Ga-68-NOTA-NI and Ga-68- SCN-NOTA-NI were labeled in high efficiency (> 96%) and were stable at room temperature in the prepared medium and at 37 degrees C in human serum. In vitro cell uptake experiments using CHO and CT-26 cell lines showed significantly increased uptakes of both of the agents in hypoxic condition. Biodistribution study in CT-26 xenografted mice showed increasing tumor to muscle ratios. Ga-68-NOTA-NI showed lower intestine uptake than Ga-68-NOTA-SCN-NI due to hydrophilicity. Also, Ga-68-NOTA-NI showed higher tumor uptake than Ga-68-NOTA-SCN-NI in an animal PET study. In conclusion, we successfully developed Ga-68 labeled NI derivatives for hypoxic tissue imaging.

引用

页码：6378 / 6385

页数：8

共 52 条

[1] 1,4,7-triazacyclononane-1-succinic acid-4,7-diacetic acid (NODASA):: a new bifunctional chelator for radio gallium-labelling of biomolecules [J].