Evaluation of [125I]IPOS as a molecular imaging probe for hypoxia-inducible factor-1-active regions in a tumor

Comparison among single-photon emission computed tomography/X-ray computed tomography imaging, autoradiography, and immunohistochemistry

Masashi Ueda, Takashi Kudo, Yasuko Mutou, Izumi Ogihara Umeda, Azusa Miyano, Kei Ogawa, Masahiro Ono, Hirofumi Fujii, Shinae Kizaka-Kondoh, Masahiro Hiraoka, Hideo Saji

Research output: Contribution to journalArticle

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Abstract

To image hypoxia-inducible factor-1 (HIF-1)-active tumors, we previously developed a chimeric protein probe ([123/125I]IPOS) that is degraded in the same manner as HIF-1α under normoxic conditions. In the present study, we aim to show that the accumulation of radioiodinated POS reflects the expression of HIF-1. In vivo single-photon emission computed tomography (SPECT)/X-ray CT (CT) imaging, autoradiography, and double-fluorescent immunostaining for HIF-1α and pimonidazole (PIMO) were carried out 24h after the injection of [125I]IPOS. Tumor metabolite analysis was also carried out. A tumor was clearly visualized by multi-pinhole, high-resolution SPECT/CT imaging with [125I]IPOS. The obtained images were in accordance with the corresponding autoradiograms and with the results of ex vivo biodistribution. A metabolite analysis revealed that 77% of the radioactivity was eluted in the macromolecular fraction, suggesting that the radioactivity mainly existed as [125I]IPOS in the tumors. Immunohistochemistry revealed that the HIF-1α-positive areas and PIMO-positive areas were not always identical, only some of the regions were positive for both markers. The areas showing [125I]IPOS accumulation were positively and significantly correlated with the HIF-1α-positive areas (R=0.75, P125I]IPOS-accumulated areas and HIF-1α-positive areas was significantly greater than that between the [125I]IPOS-accumulated areas and the PIMO-positive areas (P125I]IPOS accumulation reflects HIF-1 expression. Thus, [123/125I]IPOS can serve as a useful probe for the molecular imaging of HIF-1-active tumors.

Original languageEnglish
Pages (from-to)2090-2096
Number of pages7
JournalCancer Science
Volume102
Issue number11
DOIs
Publication statusPublished - Nov 2011
Externally publishedYes

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Hypoxia-Inducible Factor 1
Molecular Probes
Molecular Imaging
X Ray Computed Tomography
Single-Photon Emission-Computed Tomography
Autoradiography
Immunohistochemistry
Neoplasms
Radioactivity
Injections

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Evaluation of [125I]IPOS as a molecular imaging probe for hypoxia-inducible factor-1-active regions in a tumor : Comparison among single-photon emission computed tomography/X-ray computed tomography imaging, autoradiography, and immunohistochemistry. / Ueda, Masashi; Kudo, Takashi; Mutou, Yasuko; Umeda, Izumi Ogihara; Miyano, Azusa; Ogawa, Kei; Ono, Masahiro; Fujii, Hirofumi; Kizaka-Kondoh, Shinae; Hiraoka, Masahiro; Saji, Hideo.

In: Cancer Science, Vol. 102, No. 11, 11.2011, p. 2090-2096.

Research output: Contribution to journalArticle

Ueda, Masashi ; Kudo, Takashi ; Mutou, Yasuko ; Umeda, Izumi Ogihara ; Miyano, Azusa ; Ogawa, Kei ; Ono, Masahiro ; Fujii, Hirofumi ; Kizaka-Kondoh, Shinae ; Hiraoka, Masahiro ; Saji, Hideo. / Evaluation of [125I]IPOS as a molecular imaging probe for hypoxia-inducible factor-1-active regions in a tumor : Comparison among single-photon emission computed tomography/X-ray computed tomography imaging, autoradiography, and immunohistochemistry. In: Cancer Science. 2011 ; Vol. 102, No. 11. pp. 2090-2096.
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abstract = "To image hypoxia-inducible factor-1 (HIF-1)-active tumors, we previously developed a chimeric protein probe ([123/125I]IPOS) that is degraded in the same manner as HIF-1α under normoxic conditions. In the present study, we aim to show that the accumulation of radioiodinated POS reflects the expression of HIF-1. In vivo single-photon emission computed tomography (SPECT)/X-ray CT (CT) imaging, autoradiography, and double-fluorescent immunostaining for HIF-1α and pimonidazole (PIMO) were carried out 24h after the injection of [125I]IPOS. Tumor metabolite analysis was also carried out. A tumor was clearly visualized by multi-pinhole, high-resolution SPECT/CT imaging with [125I]IPOS. The obtained images were in accordance with the corresponding autoradiograms and with the results of ex vivo biodistribution. A metabolite analysis revealed that 77{\%} of the radioactivity was eluted in the macromolecular fraction, suggesting that the radioactivity mainly existed as [125I]IPOS in the tumors. Immunohistochemistry revealed that the HIF-1α-positive areas and PIMO-positive areas were not always identical, only some of the regions were positive for both markers. The areas showing [125I]IPOS accumulation were positively and significantly correlated with the HIF-1α-positive areas (R=0.75, P125I]IPOS-accumulated areas and HIF-1α-positive areas was significantly greater than that between the [125I]IPOS-accumulated areas and the PIMO-positive areas (P125I]IPOS accumulation reflects HIF-1 expression. Thus, [123/125I]IPOS can serve as a useful probe for the molecular imaging of HIF-1-active tumors.",
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