Kit formulation for preparation and biological evaluation of a novel ^99mTc-oxo complex with metronidazole xanthate for imaging tumor hypoxia

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• 作者：Zhenxiang Li^a ; Xiao Lin^a ; Junbo Zhang^a ; ^{zhjunbo@bnu.edu.cn" class="auth_mail" title="E-mail the corresponding author} ; Xuebin Wang^a ; Zhonghui Jin^b ; ^{jinzhonghui@163.com" class="auth_mail" title="E-mail the corresponding author} ; Weifang Zhang^b ; Yanyan Zhang^b
• 关键词：Metronidazole ; Xanthate ; 99mTc ; Hypoxia ; Tumor ; Imaging
• 刊名：Nuclear Medicine and Biology
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：43
• 期：2
• 页码：165-170
• 全文大小：437 K

文摘

Achieving an ideal ^99mTc labeled nitroimidazole hypoxia marker is still considered to be of great interest. Metronidazole xanthate (MNXT) ligand was synthesized and radiolabeled with ^99mTc-glucoheptonate (GH) to form the ^99mTcO-MNXT complex, for the potential use as a novel probe for imaging tumor hypoxia.

Methods

For labeling, ^99mTcO-MNXT was prepared by ligand-exchange reaction with ^99mTc-GH. The radiochemical purity of the ^99mTcO-MNXT complex was measured by thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). The distribution coefficient and stability of the complex was investigated. The structure of the ^99mTcO-MNXT complex was verified by preparation and characterization of the corresponding stable rhenium complex. The cellular uptake of the ^99mTcO-MNXT complex was determined in murine sarcoma S180 cell lines under hypoxic and aerobic conditions. The biodistribution and single photon emission computed tomography (SPECT) image studies of the ^99mTcO-MNXT complex were performed in mice bearing S 180 tumor.

Results

The radiochemical purity of the ^99mTcO-MNXT complex was over 90%. It had good in vitro stability and its distribution coefficient indicated that it was a hydrophilic complex. When ^99mTc and Re complexes were coinjected in HPLC, both radioactivity (for ^99mTc complex) and UV detectors (for Re complex) showed nearly identical HPLC profiles, suggesting their structures are similar. The tumor cell experiment and the biodistribution in mice bearing S 180 tumor showed that the ^99mTcO-MNXT complex had a good hypoxic selectivity and accumulated in the tumor with high uptake and good retention. Single photon emission computed tomography (SPECT) image studies showed that the tumor detection was observable.

Conclusions

^99mTcO-MNXT is prepared from a kit without the need for purification and shows high tumor uptake, tumor/blood and tumor/muscle ratios, suggesting that it would be a promising candidate for imaging tumor hypoxia.