期刊
RADIOTHERAPY AND ONCOLOGY
卷 92, 期 3, 页码 423-428出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.radonc.2009.06.019
关键词
Carbonic anhydrase IX (CA IX); Sulfonamide; Fluorescent imaging; Tumour hypoxia
资金
- EU 6th framework Program [2003-502932]
- EU 7th framework [2008-222741]
- Dutch Cancer Society [2008-4068]
Background and purpose: Carbonic anhydrase (CA) IX is suggested to be an endogenous market of hypoxia. Fluorescent sulfonamides with a high affinity for CA IX (CAI) have been developed and shown to bind to cells only when CA IX protein was expressed and while cells were hypoxic. The aim of this study was to investigate the in vivo CAI binding properties in a xenograft tumour model using fluorescent imaging. Materials and methods: NMRI-nu mice subcutaneously transplanted with HT-29 colorectal tumours were treated with 7% oxygen or with nicotinamide and carbogen and were compared with control animals. CAI accumulation was monitored by non-invasive fluorescent imaging. Results: Specific CAI accumulation could be observed in delineated turnout areas as compared with a non-sulfonamide analogue (P < 0.01). Administration of nicotinamide and carbogen, decreasing acute and chronic hypoxia, respectively, prevented CAI accumulation (P < 0.05). When treated with 7% oxygen breathing, a 3-fold higher CAI accumulation (P < 0.01) was observed. Furthermore, the bound CAI fraction was rapidly reduced upon turnout reoxygenation (P < 0.01). Conclusions: Our in vivo imaging results confirm previous in vitro data demonstrating that CAI binding and retention require exposure to hypoxia. Fluorescent labelled sulfonamides provide a powerful tool to visualize hypoxia response. An important step is made towards clinical applicability, indicating the potential of patient selection for CA IX-directed therapies. (C) 2009 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 92 (2009) 423-428
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