A Novel PET Probe "[18 F]DiFA" Accumulates in Hypoxic Region via Glutathione Conjugation Following Reductive Metabolism

Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging
Yoichi ShimizuYuji Kuge

Abstract

Hypoxia in tumor has close relationship with angiogenesis and tumor progression. Previously, we developed 2,2-dihydroxymethyl-3-[18F]fluoropropyl-2-nitroimidazole ([18F]DiFA) as a novel positron emission tomography (PET) probe for diagnosis of hypoxia. In this study, we elucidated whether the accumulation of [18F]DiFA in cells is dependent on the hypoxic state and revealed how [18F]DiFA accumulates in hypoxic cells in combination with imaging mass spectrometry (IMS). FaDu human head and neck cancer cells were treated with [18F]DiFA and then incubated under normoxia (21% O2) or hypoxia (1% O2) for 2 h. The cells were extracted using methanol, and the radioactivities of the precipitates (macromolecule fraction) and supernatants (low-molecular-weight fraction) were measured. FaDu-bearing mice were injected intravenously with [18F]DiFA and with pimonidazole 1 h later. The tumors were excised 2 h after the injection of [18F]DiFA. Autoradiography, IMS, and immunohistochemical (IHC) staining for pimonidazole were performed with serial tumor sections. In the in vitro study, the radioactivity of FaDu cells was significantly higher under hypoxia than that under normoxia (0.53 ± 0.02 vs. 0.27 ± 0.02 %dose/mg protein, p < 0.05). The radioa...Continue Reading

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Citations

Nov 2, 2018·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Yoichi Shimizu
Jul 2, 2020·Organic & Biomolecular Chemistry·Jie GaoXianfeng Gu
Oct 29, 2021·Journal of Medicinal Chemistry·Hiroyuki SuzukiYasushi Arano

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