Optical imaging of CCK₂/gastrin receptor-positive tumors with a minigastrin near-infrared probe.

Abstract

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.

• Authors: Elisabeth Laabs, Martin Béhé, Susanne Kossatz, Wilhelm Frank, Werner A Kaiser, Ingrid Hilger
• Journal: Investigative radiology (Invest Radiol) Vol. 46 Issue 3 Pg. 196-201 (Mar 2011) ISSN: 1536-0210 [Electronic] United States
• PMID: 21139504 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Gastrins
• RNA, Messenger
• Receptor, Cholecystokinin B
• minigastrin

Topics

• Animals
• Disease Models, Animal
• Feasibility Studies
• Flow Cytometry
• Gastrins
• HT29 Cells (metabolism)
• Humans
• Mice
• Mice, Inbred BALB C
• Neoplasms (diagnosis, pathology)
• RNA, Messenger
• Receptor, Cholecystokinin B (metabolism)