title: 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.
abstract: 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.
authors.affiliation: Radioisotopes Research Laboratory, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Ueda
authors.forename: Takashi
authors.initials: T
authors.lastname: Kudo
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Mutou
authors.forename: Izumi Ogihara
authors.initials: IO
authors.lastname: Umeda
authors.forename: Azusa
authors.initials: A
authors.lastname: Miyano
authors.forename: Kei
authors.initials: K
authors.lastname: Ogawa
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ono
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Fujii
authors.forename: Shinae
authors.initials: S
authors.lastname: Kizaka-Kondoh
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hiraoka
authors.forename: Hideo
authors.initials: H
authors.lastname: Saji
mesh_terms: D000818:Animals; D001345:Autoradiography; D001710:Biotin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005260:Female; D019085:Fluorescent Antibody Technique, Direct; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis*; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D008325:Mammary Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D009363:Neoplasm Proteins / Q000032:analysis*; D009593:Nitroimidazoles / Q000032:analysis; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D011993:Recombinant Fusion Proteins / Q000493:pharmacokinetics; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*; D014057:Tomography, X-Ray Computed
chemical_list: C568655:3-(iodobenzoyl)norbiotinamide-PTD-ODD-SAV fusion protein; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007457:Iodine Radioisotopes; D009363:Neoplasm Proteins; D009593:Nitroimidazoles; D019275:Radiopharmaceuticals; D011993:Recombinant Fusion Proteins; C033815:pimonidazole; D001710:Biotin