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Receptor-targeted optical imaging of tumors with near-infrared fluorescent ligands

Nature Biotechnology volume 19, pages 327–331 (2001)Cite this article

Abstract

We report here the in vivo diagnostic use of a peptide–dye conjugate consisting of a cyanine dye and the somatostatin analog octreotate as a contrast agent for optical tumor imaging. When used in whole-body in vivo imaging of mouse xenografts, indotricarbocyanine-octreotate accumulated in tumor tissue. Tumor fluorescence rapidly increased and was more than threefold higher than that of normal tissue from 3 to 24 h after application. The targeting conjugate was also specifically internalized by primary human neuroendocrine tumor cells. This imaging approach, combining the specificity of ligand/receptor interaction with near-infrared fluorescence detection, may be applied in various other fields of cancer diagnosis.

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Figure 1: Chemical nature of the conjugates.
Figure 2: Specific binding and endocytosis of the IDCC-labeled octreotate.
Figure 3: Internalization and cellular retention as measured by flow cytometry.
Figure 4: Specific and long-lasting in vivo targeting of tumors.
Figure 5: Microscopic analysis of nude mouse tumor tissue sections 6 h after injection of the targeting conjugate.
Figure 6: Internalization of IDCC-octreotate into human neuroendocrine tumor cells ex vivo.

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Acknowledgements

We thank Yvonne Giesecke, Michaela Nieter, Christiane Rheinländer, Udo Swiderski, and Stefan Wisniewski for excellent technical assistance. This study was supported in part by the Bundesministerium für Bildung und Forschung (0310941) and the Deutsche Forschungsgemeinschaft (SFB 366/A5, TFB 17).

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Author notes

  1. Andreas Becker and Carsten Hessenius: These authors contributed equally to this work.

Authors and Affiliations

  1. Institut für Diagnostikforschung GmbH an der Freien Universität Berlin, Berlin, 14050, Germany

    Andreas Becker, Kai Licha & Wolfhard Semmler

  2. Universitätsklinikum Charité der Humboldt Universität zu Berlin, Campus Virchow-Klinikum, Medizinische Klinik m.S. Hepatologie und Gastroenterologie, Berlin, 13353, Germany

    Carsten Hessenius, Bertram Wiedenmann & Carsten Grötzinger

  3. Physikalisch-Technische Bundesanstalt, Berlin, 10587, Germany

    Bernd Ebert & Uwe Sukowski

  4. Deutsches Krebsforschungszentrum, Heidelberg, 69120, Germany

    Wolfhard Semmler

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Correspondence to Bertram Wiedenmann.

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Becker, A., Hessenius, C., Licha, K. et al. Receptor-targeted optical imaging of tumors with near-infrared fluorescent ligands. Nat Biotechnol 19, 327–331 (2001). https://doi.org/10.1038/86707

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