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.
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: Jyoti Roy; Karson S Putt; Domenico Coppola; Marino E Leon; Farah K Khalil; Barbara A Centeno; Noel Clark; Valerie E Stark; David L Morse; Philip S Low Journal: Oncotarget Date: 2016-03-22
Authors: Francesco Conversano; Giulia Soloperto; Antonio Greco; Andrea Ragusa; Ernesto Casciaro; Fernanda Chiriacò; Christian Demitri; Giuseppe Gigli; Alfonso Maffezzoli; Sergio Casciaro Journal: Int J Nanomedicine Date: 2012-08-09