Yi Xiaomin, Yan Fei, Wang Fuli, Qin Weijun, Wu Guojun, Yang Xiaojian, Shao Chen, Chung Leland W K, Yuan Jianlin
Department of Urology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China (mainland).
Department of Medicine, Uro-Oncology Research Program, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Med Sci Monit. 2015 Feb 16;21:511-7. doi: 10.12659/MSM.892437.
The aim of this study was to investigate near-infrared fluorescence (NIRF) imaging as a novel imaging modality that allows for early detection of cancer and real-time monitoring to acquire related information. IR-780 iodide, a lipophilic dye, accumulates selectively in breast cancer cells and drug-resistant human lung cancer cells, with a peak emission at 780 nm that can be easily detected by the NIRF imaging system. The application of IR-780 for prostate cancer imaging was thoroughly investigated to further expand its clinical value.
The impact of IR-780 on the survival of prostate cancer cells PC-3 and LNCaP as well as normal prostate epithelial cells RWPE-1 was determined. Duration of IR-780 dye staining was optimized in PC-3 cells. The involvement of specific OATP1B3 inhibitor in the selective accumulation of IR-780 was investigated. IR-780 for prostate cancer imaging was carried out in athymic nude mouse models and, acute toxicity of IR-780 was evaluated.
IR-780 incubation resulted in a dose-dependent inhibition to cell proliferation. Mean fluorescence intensity of prostate cancer cells peaked at 20-min IR-780 incubation. Specific uptake of IR-780 dye in prostate cancer cells was mainly through the function of OATP1B3. We also demonstrated that NIRF dye effectively identified the subcutaneous prostate cancer xenografts, subsequently confirmed by histological examination. There was no significant impact on the physical activity, weight, and tissue histology of BABL/C mice with 10-fold imaging dose of 1-month IR-780 dye administration.
NIRF imaging using IR-780 dye is a feasible and practicable method for prostate cancer detection, with potential tumor-killing ability, although more investigations are needed before clinical translation.
本研究旨在探讨近红外荧光（NIRF）成像作为一种新型成像方式，用于癌症的早期检测和实时监测以获取相关信息。亲脂性染料碘化铱（IR）-780选择性地积聚在乳腺癌细胞和耐药性人肺癌细胞中，在780nm处有一个发射峰，可被NIRF成像系统轻松检测到。对IR-780在前列腺癌成像中的应用进行了深入研究，以进一步扩大其临床价值。
测定了IR-780对前列腺癌细胞PC-3和LNCaP以及正常前列腺上皮细胞RWPE-1存活的影响。在PC-3细胞中优化了IR-780染料染色的持续时间。研究了特异性有机阴离子转运多肽1B3（OATP1B3）抑制剂在IR-780选择性积聚中的作用。在无胸腺裸鼠模型中进行了IR-780用于前列腺癌成像的研究，并评估了IR-780的急性毒性。
IR-780孵育导致对细胞增殖的剂量依赖性抑制。前列腺癌细胞的平均荧光强度在IR-780孵育20分钟时达到峰值。IR-780染料在前列腺癌细胞中的特异性摄取主要通过OATP1B3的功能实现。我们还证明，NIRF染料有效地识别了皮下前列腺癌异种移植瘤，随后经组织学检查证实。给予1个月的IR-780染料成像剂量的10倍，对BABL/C小鼠的身体活动、体重和组织组织学没有显著影响。
使用IR-780染料的NIRF成像对于前列腺癌检测是一种可行且实用的方法，具有潜在的肿瘤杀伤能力，尽管在临床转化之前还需要更多的研究。
