Phosphorescent light-emitting iridium complexes serve as a hypoxia-sensing probe for tumor imaging in living animals
Phosphorescent light-emitting iridium complexes serve as a hypoxia-sensing probe for tumor imaging in living animals
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DOI：
10.1117/12.855704
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发表时间：
2010-02
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影响因子：
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通讯作者：
T. Takeuchi;Shaojuan Zhang;K. Negishi;Toshitada Yoshihara;M. Hosaka;S. Tobita
中科院分区：
文献类型：
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作者：
T. Takeuchi;Shaojuan Zhang;K. Negishi;Toshitada Yoshihara;M. Hosaka;S. Tobita
铱复合体是一种很有前途的有机发光二极管材料，可用于下一代电视和电脑显示器，它能发出磷光。磷光被氧猝灭。我们使用这种氧猝灭特征来成像肿瘤缺氧。红色发光铱配合物Ir(btp)2(acac) （btp）在培养细胞系中呈现缺氧依赖性发光，其发光强度与缺氧诱导因子(HIF)-1的表达平行。BTP进一步应用于5个裸鼠移植瘤的成像。所有肿瘤早在注射后5分钟就出现明亮的btp发射图像。BTP依赖性肿瘤图像在注射后1 ~ 2h达到峰值，并在24h内从肿瘤中移除。BTP图像识别的最小尺寸至少为直径2mm。通过形态学检查和磷光寿命测定，推测BTP定位于肿瘤细胞，而不是通过与白蛋白结合而停留在肿瘤微血管中。发光探针用于肿瘤成像的主要问题是其对皮肤表面深层组织的外显性弱。由于BTP易于修改，我们制作了具有较长激发/发射波长的BTP类似物，以提高组织外显率。其中，BTPHSA显示560/720波长，并描绘了从皮肤表面6- 7mm深的肿瘤移植的清晰成像。我们认为BTP类似物在低氧病变（如肿瘤组织）成像方面具有巨大的潜力。
Iridium complex, a promising organic light-emitting diode material for next generation television and computer displays, emits phosphorescence. Phosphorescence is quenched by oxygen. We used this oxygen-quenching feature for imaging tumor hypoxia. Red light-emitting iridium complex Ir(btp)2(acac) (BTP) presented hypoxia-dependent light emission in culture cell lines, whose intensity was in parallel with hypoxia-inducible factor (HIF)-1 expression. BTP was further applied to imaging five nude mouse-transplanted tumors. All tumors presented a bright BTP-emitting image as early as 5 min after the injection. The BTP-dependent tumor image peaked at 1 to 2 h after the injection, and was then removed from tumors within 24 h. The minimal BTP image recognition size was at least 2 mm in diameter. By morphological examination and phosphorescence lifetime measurement, BTP is presumed to localize to the tumor cells, not to stay in the tumor microvessels by binding to albumin. The primary problem on suse of luminescent probe for tumor imaging is its weak penetrance to deep tissues from the skin surface. Since BTP is easily modifiable, we made BTP analogues with a longer excitation/emission wavelength to improve the tissue penetrance. One of them, BTPHSA, displayed 560/720 wavelength, and depicted its clear imaging from tumors transplanted over 6-7 mm deep from the skin surface. We suggest that BTP analogues have a vast potential for imaging hypoxic lesions such as tumor tissues.