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Optical Imaging of CCK2/Gastrin Receptor-Positive Tumors With a Minigastrin Near-Infrared Probe

Laabs, Elisabeth MD*; Béhé, Martin PhD; Kossatz, Susanne MS*; Frank, Wilhelm PhD; Kaiser, Werner A. MD, MS*; Hilger, Ingrid PhD*

doi: 10.1097/RLI.0b013e3181fef020
Original Article
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Purpose: A variety of tumors in different organs with good accessibility to near-infrared light express the cholecystokinin-2 (CCK2)/gastrin receptor. Therefore, the applicability of fluorescence optical imaging was assessed using a novel peptide probe.

Materials and Methods: This study was approved by the regional animal committee. Our optical peptide probe (DY-minigastrin) was synthesized by coupling a hemicyanine dye to a gastrin derivative peptide (minigastrin). In vitro CCK2/gastrin receptor identification was performed in receptor-positive HT-29 and negative A-375 cells using flow cytometry, laser scanning microscopy, and macroscopic near-infrared fluorescent (NIRF) imaging. For in vivo studies, tumor cells were implanted into mice, and DY-minigastrin in presence or absence of nonlabeled minigastrin (control of signaling specificity) was applied intravenously. Fluorescence signals in tumors and organs were recorded and statistically analyzed.

Results: Flow cytometry, laser scanning microscopy, and in vitro macroscopic imaging of cell pellets revealed a distinct accumulation of our minigastrin probe in HT-29 cells, showing distinct probe internalization. In vivo NIRF whole-body animal imaging, again, demonstrated a clear depiction of HT-29 tumors, which was reversed by blocking with nonlabeled minigastrin. Semi-quantitative fluorescence analysis and histologic observations were in agreement with these observations. A distinct probe organ distribution was observed.

Conclusions: Our observations indicate that DY-minigastrin-based NIRF optical imaging of CCK2/gastrin receptor protein is feasible. Because of its widespread occurrence in different tumor types, endoscopic, laparoscopic, and tomographic receptor imaging could be accomplished in the near future.

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From the *Department of Experimental Radiology, Institute of Diagnostic and Interventional Radiology, University Hospital Jena, Jena, Germany; †Department of Nuclear Medicine, University of Freiburg, Freiburg, Germany; and ‡Dyomics GmbH, Jena, Germany.

Received March 19, 2010, and accepted for publication, after revision, August 28, 2010.

Supported in parts by the German Ministry of Education and Research (BMBF, project 13N10287).

Reprints: Ingrid Hilger, PhD, AG Experimentelle Radiologie, Institut für Diagnostische und Interventionelle Radiologie, Universitätsklinikum Jena, Erlanger Allee 111, D-07747 Jena, Germany. E-mail: ingrid.hilger@med.uni-jena.de.

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© 2011 Lippincott Williams & Wilkins, Inc.