TY - JOUR
T1 - Evaluation of [125I]IPOS as a molecular imaging probe for hypoxia-inducible factor-1-active regions in a tumor
T2 - Comparison among single-photon emission computed tomography/X-ray computed tomography imaging, autoradiography, and immunohistochemistry
AU - Ueda, Masashi
AU - Kudo, Takashi
AU - Mutou, Yasuko
AU - Umeda, Izumi Ogihara
AU - Miyano, Azusa
AU - Ogawa, Kei
AU - Ono, Masahiro
AU - Fujii, Hirofumi
AU - Kizaka-Kondoh, Shinae
AU - Hiraoka, Masahiro
AU - Saji, Hideo
N1 - Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.
PY - 2011/11
Y1 - 2011/11
N2 - 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, P<0.0001). The correlation coefficient between [125I]IPOS-accumulated areas and HIF-1α-positive areas was significantly greater than that between the [125I]IPOS-accumulated areas and the PIMO-positive areas (P<0.01). These findings indicate that [125I]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.
AB - 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, P<0.0001). The correlation coefficient between [125I]IPOS-accumulated areas and HIF-1α-positive areas was significantly greater than that between the [125I]IPOS-accumulated areas and the PIMO-positive areas (P<0.01). These findings indicate that [125I]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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U2 - 10.1111/j.1349-7006.2011.02057.x
DO - 10.1111/j.1349-7006.2011.02057.x
M3 - Article
C2 - 21824221
AN - SCOPUS:80055011150
VL - 102
SP - 2090
EP - 2096
JO - Cancer Science
JF - Cancer Science
SN - 1347-9032
IS - 11
ER -