title: Phosphorescent light-emitting iridium complexes serve as a hypoxia-sensing probe for tumor imaging in living animals.
abstract: Iridium complex is a promising organic light-emitting diode material for next generation video displays that emits phosphorescence quenched by oxygen. We used this oxygen-quenching feature for imaging tumor hypoxia. Red light-emitting Ir(btp)(2)(acac) (BTP) presented hypoxia-dependent light emission in culture cell lines, whose intensity was in parallel with hypoxia-inducible factor-1alpha images. BTP was further applied to imaging five nude mouse transplanted with tumors. All tumors presented a bright BTP-emitting image even 5 minutes after injection. The minimal image recognition size was approximately 2 mm in diameter. By morphologic examination and phosphorescence lifetime measurement, BTP appeared to localize to the tumor cells. Because BTP is easily modifiable, we synthesized BTP analogues with a longer excitation/emission wavelength. One of them, BTPHSA, depicted clear imaging from tumors transplanted 6 to 7 mm deep from the skin surface. We suggest that iridium complex materials have a vast potential for imaging hypoxic lesions such as tumor tissues.
authors.affiliation: Secretion Biology Laboratory, Institute for Molecular and Cellular Regulation and Division of Diagnostic Radiology and Nuclear Medicine, Graduate School of Medical Sciences, Gunma University, Maebashi, Japan.
authors.forename: Shaojuan
authors.initials: S
authors.lastname: Zhang
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hosaka
authors.forename: Toshitada
authors.initials: T
authors.lastname: Yoshihara
authors.forename: Kazuya
authors.initials: K
authors.lastname: Negishi
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Iida
authors.forename: Seiji
authors.initials: S
authors.lastname: Tobita
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takeuchi
mesh_terms: D000818:Animals; D016466:CHO Cells; D015687:Cell Hypoxia / Q000502:physiology; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D019073:HT29 Cells; D006367:HeLa Cells; D006801:Humans; D007495:Iridium / Q000737:chemistry; D008163:Luminescent Measurements / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000378:metabolism; D009942:Organometallic Compounds / Q000737:chemistry / Q000493:pharmacokinetics; D010100:Oxygen / Q000097:blood / Q000378:metabolism; D010313:Partial Pressure; D055668:Photochemical Processes; D011725:Pyridines / Q000737:chemistry; D013876:Thiophenes / Q000737:chemistry; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
chemical_list: D009942:Organometallic Compounds; D011725:Pyridines; D013876:Thiophenes; D007495:Iridium; D010100:Oxygen