Format

Send to

Choose Destination
Radiother Oncol. 2009 Sep;92(3):423-8. doi: 10.1016/j.radonc.2009.06.019. Epub 2009 Jul 16.

Imaging of CA IX with fluorescent labelled sulfonamides distinguishes hypoxic and (re)-oxygenated cells in a xenograft tumour model.

Author information

1
Maastricht Radiation Oncology (MaastRO) Lab, GROW-School for Oncology and Developmental Biology, University of Maastricht, The Netherlands. ludwig.dubois@maastro.unimaas.nl

Abstract

BACKGROUND AND PURPOSE:

Carbonic anhydrase (CA) IX is suggested to be an endogenous marker 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 tumour 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 tumour 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.

PMID:
19616332
DOI:
10.1016/j.radonc.2009.06.019
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center