Open AccessEvaluation of [ 125 I]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
Author(s) -
Ueda Masashi,
Kudo Takashi,
Mutou Yasuko,
Umeda Izumi Ogihara,
Miyano Azusa,
Ogawa Kei,
Ono Masahiro,
Fujii Hirofumi,
KizakaKondoh Shinae,
Hiraoka Masahiro,
Saji Hideo
Publication year - 2011
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2011.02057.x
Subject(s) - immunostaining , in vivo , immunohistochemistry , single photon emission computed tomography , nuclear medicine , hypoxia (environmental) , ex vivo , metabolite , pathology , biodistribution , biology , chemistry , medicine , oxygen , endocrinology , microbiology and biotechnology , organic chemistry
To image hypoxia‐inducible factor‐1 (HIF‐1)‐active tumors, we previously developed a chimeric protein probe ([ 123/125 I]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 24 h after the injection of [ 125 I]IPOS. Tumor metabolite analysis was also carried out. A tumor was clearly visualized by multi‐pinhole, high‐resolution SPECT/CT imaging with [ 125 I]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 [ 125 I]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 [ 125 I]IPOS accumulation were positively and significantly correlated with the HIF‐1α‐positive areas ( R = 0.75, P < 0.0001). The correlation coefficient between [ 125 I]IPOS‐accumulated areas and HIF‐1α‐positive areas was significantly greater than that between the [ 125 I]IPOS‐accumulated areas and the PIMO‐positive areas ( P < 0.01). These findings indicate that [ 125 I]IPOS accumulation reflects HIF‐1 expression. Thus, [ 123/125 I]IPOS can serve as a useful probe for the molecular imaging of HIF‐1‐active tumors. ( Cancer Sci 2011; 102: 2090–2096)