title: Radiolabeled probes targeting hypoxia-inducible factor-1-active tumor microenvironments.
abstract: Because tumor cells grow rapidly and randomly, hypoxic regions arise from the lack of oxygen supply in solid tumors. Hypoxic regions in tumors are known to be resistant to chemotherapy and radiotherapy. Hypoxia-inducible factor-1 (HIF-1) expressed in hypoxic regions regulates the expression of genes related to tumor growth, angiogenesis, metastasis, and therapy resistance. Thus, imaging of HIF-1-active regions in tumors is of great interest. HIF-1 activity is regulated by the expression and degradation of its α subunit (HIF-1α), which is degraded in the proteasome under normoxic conditions, but escapes degradation under hypoxic conditions, allowing it to activate transcription of HIF-1-target genes. Therefore, to image HIF-1-active regions, HIF-1-dependent reporter systems and injectable probes that are degraded in a manner similar to HIF-1α have been recently developed and used in preclinical studies. However, no probe currently used in clinical practice directly assesses HIF-1 activity. Whether the accumulation of (18)F-FDG or (18)F-FMISO can be utilized as an index of HIF-1 activity has been investigated in clinical studies. In this review, the current status of HIF-1 imaging in preclinical and clinical studies is discussed.
authors.affiliation: Department of Pharmaceutical Analytical Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan.
authors.forename: Masashi
authors.identifier: 0000-0001-7027-1568
authors.initials: M
authors.lastname: Ueda
authors.affiliation: Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.
authors.forename: Hideo
authors.identifier: 0000-0002-3077-9321
authors.initials: H
authors.lastname: Saji
mesh_terms: D000818:Animals; D015870:Gene Expression; D017930:Genes, Reporter; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D057054:Molecular Imaging; D015335:Molecular Probes / Q000378:metabolism*; D009369:Neoplasms / Q000175:diagnosis / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000378:metabolism*; D059016:Tumor Microenvironment / Q000235:genetics
chemical_list: D051793:Hypoxia-Inducible Factor 1; D015335:Molecular Probes; D019275:Radiopharmaceuticals; D010100:Oxygen