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KMID : 1145520190050020101
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Journal of Radiopharmaceuticals and Molecular Probes
2019 Volume.5 No. 2 p.101 ~ p.112
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Comparative study of 2-nitroimidazole-fluorophore-conjugated derivatives with pimonidazole for imaging tumor hypoxia
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Seelam Sudhakara Reddy
Hong Mi-Kyung
Lee Yun-Sang
Jeong Jae-Min
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Abstract
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Herein, 2-nitroimidazole-fluorophore conjugates were synthesized by linking 2-nitroimidazole and FITCor RITC via thiourea bonds. The prepared derivatives were stable for 2 h in Dulbecco’s modified Eagle’smedium (DMEM) at 37 °C. The novel conjugates were studied for their in vitro uptake under hypoxic conditionsusing U87MG and CT-26 cell lines, showing significantly higher uptakes in hypoxic than normoxic cells.
Immunohistochemical analysis confirmed hypoxia in U87MG and CT-26 xenografted tumor tissues. Moreover,the prepared conjugates were evaluated by in vivo experiments after intravenous injection in U87MG andCT-26 xenografted mice. Hypoxia was confirmed by immunohistochemistry of the prepared derivatives withco-injected pimonidazole. Confocal microscopy of the prepared derivatives showed strong fluorescence inhypoxic tumor tissues correlated with the pimonidazole distribution. This suggested that the 2-nitroimidazolefluorophoreconjugates are promising optical imaging probes for tumor hypoxia and are promising substitutesfor pimonidazole immunohistochemistry, which requires a multi-step procedure of incubation involving antibody,second antibody, dye, hydrogen peroxide, and multiple washing steps.
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KEYWORD
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FITC, RITC, immunohistochemistry, hypoxia, 2-nitroimidazole-FITC, and 2-nitroimidazole-RITC
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