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

Cited 46 time in Web of Science Cited 47 time in Scopus
Authors
Hoigebazar, Lathika; Jeong, Jae Min; Choi, Soo Young; Choi, Jae Yeon; Lee, Yun-Sang; Chung, June-Key; Chung, Young Keun; Lee, Myung Chul; Lee, Dong Soo; Shetty, Dinesh
Issue Date
2010-09-09
Publisher
AMER CHEMICAL SOC
Citation
JOURNAL OF MEDICINAL CHEMISTRY; Vol.53 17; 6378-6385
Abstract
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 (68)Ga and found that both (68)Ga-NOTA-NI and (68)Ga- 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. (68)Ga-NOTA-NI showed lower intestine uptake than (68)Ga-NOTA-SCN-NI due to hydrophilicity. Also, (68)Ga-NOTA-NI showed higher tumor uptake than (68)Ga-NOTA-SCN-NI in an animal PET study. In conclusion, we successfully developed (68)Ga labeled NI derivatives for hypoxic tissue imaging.
ISSN
0022-2623
Language
English
URI
http://hdl.handle.net/10371/78292
DOI
https://doi.org/10.1021/jm100545a
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College of Medicine/School of Medicine (의과대학/대학원)Nuclear Medicine (핵의학전공)Journal Papers (저널논문_핵의학전공)
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