[Development of a method of high-contrasted nuclear medical imaging of hypoxia-inducible factor-1-active tumor by using a pretargeting approach].
In solid tumors, hypoxic regions arise because of an imbalance between oxygen supply and consumption. The transcription factor hypoxia-inducible factor-1 (HIF-1), which is overexpressed in hypoxic regions, was recently reported to be a master transcriptional activator of various genes (such as those involved in glucose metabolism, vascularization, invasion, and metastasis) related to malignant phenotypes. Therefore, the development of techniques for the noninvasive detection of HIF-1-active hypoxic tumor cells is of great interest. Although various modalities are used for molecular imaging in vivo, nuclear medical imaging, which can give information about organ functions, plays a central quantitative role in molecular imaging. However, because radioactive probes become attenuated due to the nuclide-specific half-life, an appropriate probe design and/or imaging method is required to obtain a high-contrasted image within a limited time. My colleagues and I have developed a probe and a method for the rapid detection of HIF-1-active hypoxic regions in tumors. Because the α subunit of HIF-1 (HIF-1α) controls the transcriptional activity of HIF-1 and is unique in that its degradation is regulated by the oxygen partial pressure, we first developed a fusion protein probe that is degraded similarly as HIF-1α. Then, to control the biodistribution of radioactivity, we utilized a "pretargeting method" that uses a combination of the fusion protein and a small-molecule radioactive probe that can bind to the protein and is rapidly cleared from the blood. Rapid and high-contrast imaging of HIF-1-active tumors can be achieved with this pretargeting method.
Radioisotopes Research Laboratory, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Japan. uedama@kuhp.kyoto-u.ac.jp
Masashi
M
Ueda
D000818:Animals; D005462:Fluorine Radioisotopes; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism / Q000502:physiology; D051379:Mice; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods*; D034702:RNA-Binding Protein FUS; D019275:Radiopharmaceuticals; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
D005462:Fluorine Radioisotopes; D051793:Hypoxia-Inducible Factor 1; D034702:RNA-Binding Protein FUS; D019275:Radiopharmaceuticals