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Proceedings Paper

Novel receptor-targeted contrast agents for optical imaging of tumors
Author(s): Andreas Becker; Carsten Hessenius; Sarah Bhargava; Bernd Ebert; Uwe Sukowski; Herbert H. Rinneberg; Bertram Wiedenmann; Wolfhard Semmler; Kai Licha
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Paper Abstract

Many gastroenteropancreatic tumors express receptors for somatostatin (SST) and/or vasoactive intestinal peptide (VIP). These receptors can be used as molecular targets for the delivery of contrast agents for tumor diagnostics. We have synthesized conjugates consisting of a cyanine dye and an SST analogue or VIP for use as contrast agents in optical imaging. Receptor binding and internalization of these compounds were examined with optical methods in transfected RIN38 tumor cells expressing the SST2 receptor or a GFP- labeled VIP (VPAC1) receptor. Furthermore, biodistribution of the conjugates was examined by laser-induced fluorescence imaging in nude mice bearing SST2 or VPAC1 receptor- expressing tumors. After incubation of RIN38 SSTR2 cells in the presence of 100 nM indotricarbocyanine-SST analogue, cell-associated fluorescence increased, whereas no increase was observed when receptor-medicated endocytosis was inhibited. Indodicarbocyanine-VIP accumulated in RIN38 VPAC1 cells and co-localization with the GFP-labeled VPAC1 receptor was observed. After injection of indotricarbocyanine-SST analogue into tumor-bearing nude mice, SST2 receptor-positive tumors could be visualized for a time period from 10 min to at least 48 h. After application of indodicarbocyanine-VIP, a fluorescence signal in VIP1 receptor-expressing tumors was only detected during the first hour. We conclude that cyanine dye-labeled VIP and SST analogue are novel, targeted contrast agents for the optical imaging of tumors expressing the relevant receptor.

Paper Details

Date Published: 26 April 2000
PDF: 7 pages
Proc. SPIE 3924, Molecular Imaging: Reporters, Dyes, Markers, and Instrumentation, (26 April 2000); doi: 10.1117/12.384238
Show Author Affiliations
Andreas Becker, Freie Univ. Berlin (Germany)
Carsten Hessenius, Humboldt Univ. zu Berlin (Germany)
Sarah Bhargava, Humboldt Univ. zu Berlin (Germany)
Bernd Ebert, Physikalisch-Technische Bundesanstalt (Germany)
Uwe Sukowski, Physikalisch-Technische Bundesanstalt (Germany)
Herbert H. Rinneberg, Physikalisch-Technische Bundesanstalt (Germany)
Bertram Wiedenmann, Humboldt Univ. zu Berlin (Germany)
Wolfhard Semmler, Freie Univ. Berlin (Germany)
Kai Licha, Freie Univ. Berlin (Germany)

Published in SPIE Proceedings Vol. 3924:
Molecular Imaging: Reporters, Dyes, Markers, and Instrumentation
Darryl J. Bornhop; Kai Licha, Editor(s)

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