Intraoperative Localization of Rectal Tumors Using Liposomal Indocyanine Green.
BACKGROUND
Tumor localization may pose a significant challenge during minimally invasive rectal resection. Near-infrared (NIR) imaging can penetrate biological tissue and afford tumor localization from the external surface of the rectum. Our aim was to develop an NIR-based tool for rectal tumor imaging that can be administered intravenously.


METHODS
We prepared indocyanine-green (ICG)-loaded liposomes by sonication. Liposomes were evaluated for their size and morphology. We then used an endoscopically induced rectal cancer in mice as a model for rectal cancer. After intravenous administration, tumors were evaluated for their fluorescence intensity. Tumor intensity was expressed in relation to the background signal, that is, tumor to background ratio (TBR).


RESULTS
Liposomes in various sizes could be prepared by adjusting sonication time. We selected 100-nm-sized liposomes for further experiments. Transmission electron microscopy showed spherical particles and confirmed the size measurements. The liposomes could be lyophilized and then rehydrated again before use without compromising their structure or signal. Fluorescence intensity was kept for 24 hours after solubilization. Testing the optimal time course for rectal tumor imaging revealed that early time course (up to 3 hours) yielded nonspecific imaging, whereas after long time course (24 hours), a very weak signal remained in the tissue. The optimal time window for imaging was after 12 hours from injection, with TBR = 8.1 ± 3.6 ( P = .002). Free ICG could not achieve similar results.


CONCLUSIONS
The liposomal ICG can be reproducibly prepared and kept in lyophilized form. Liposomal ICG could serve as a tool for intraoperative tumor localization.
1 Casali Center for Applied Chemistry, Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel.
Shlomo
S
Magdassi
2 Laboratory of Surgical Oncology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.
Shoshi
S
Bar-David
3 Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Yael
Y
Friedman-Levi
4 Research Center for Digestive Tract and Liver Diseases, Tel-Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Ehud
E
Zigmond
4 Research Center for Digestive Tract and Liver Diseases, Tel-Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Chen
C
Varol
2 Laboratory of Surgical Oncology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.|5 Department of Surgery A, Division of surgery, Tel-Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Guy
G
Lahat
2 Laboratory of Surgical Oncology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.|5 Department of Surgery A, Division of surgery, Tel-Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Joseph
J
Klausner
3 Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Sara
S
Eyal
2 Laboratory of Surgical Oncology, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.|5 Department of Surgery A, Division of surgery, Tel-Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Eran
E
Nizri
D000818:Animals; D004195:Disease Models, Animal; D007208:Indocyanine Green / Q000627:therapeutic use*; D010535:Laparoscopy / Q000379:methods*; D008081:Liposomes / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D012004:Rectal Neoplasms / Q000000981:diagnostic imaging* / Q000601:surgery*; D019265:Spectroscopy, Near-Infrared; D025321:Surgery, Computer-Assisted / Q000379:methods*
D008081:Liposomes; D007208:Indocyanine Green
indocyanine green; laparoscopic resection; liposomes; near infrared imaging; rectal adenocarcinoma