Journal of Radiopharmaceuticals and Molecular Probes (대한방사성의약품학회지)

Korean Society of Radiopharmaceuticals and Molecular Probes (대한방사성의약품학회)
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Comparative study of 2-nitroimidazole-fluorophore-conjugated derivatives with pimonidazole for imaging tumor hypoxia

  • Seelam, Sudhakara Reddy (Department of Nuclear Medicine, Institute of Radiation Medicine, Seoul National University College of Medicine) ;
  • Hong, Mi Kyung (Department of Nuclear Medicine, Institute of Radiation Medicine, Seoul National University College of Medicine) ;
  • Lee, Yun-Sang (Department of Nuclear Medicine, Institute of Radiation Medicine, Seoul National University College of Medicine) ;
  • Jeong, Jae Min (Department of Nuclear Medicine, Institute of Radiation Medicine, Seoul National University College of Medicine)
  • Received : 2019.12.12
  • Accepted : 2019.12.28
  • Published : 2019.12.30
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Abstract

Herein, 2-nitroimidazole-fluorophore conjugates were synthesized by linking 2-nitroimidazole and FITC or RITC via thiourea bonds. The prepared derivatives were stable for 2 h in Dulbecco's modified Eagle's medium (DMEM) at 37 ℃. The novel conjugates were studied for their in vitro uptake under hypoxic conditions using 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 and CT-26 xenografted mice. Hypoxia was confirmed by immunohistochemistry of the prepared derivatives with co-injected pimonidazole. Confocal microscopy of the prepared derivatives showed strong fluorescence in hypoxic tumor tissues correlated with the pimonidazole distribution. This suggested that the 2-nitroimidazole-fluorophore conjugates are promising optical imaging probes for tumor hypoxia and are promising substitutes for pimonidazole immunohistochemistry, which requires a multi-step procedure of incubation involving antibody, second antibody, dye, hydrogen peroxide, and multiple washing steps.

Keywords

References

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