Evaluation of the novel near-infrared fluorescence tracers pullulan polymer nanogel and indocyanine green/γ-glutamic acid complex for sentinel lymph node navigation surgery in large animal models.
BACKGROUND
This study aimed to examine tracers designed to overcome the disadvantages of indocyanine green (ICG), which disperses quickly to multiple lymph nodes, using a near-infrared (NIR) imaging system in animal models.


METHODS
Diluted ICG, ICG/poly-γ-glutamic acid (PGA) complex, and IRDye900-conjugated pullulan-cholesterol nanoprobe "near-infrared polynagogel" (NIR-PNG) were injected into the stomachs of dogs and pigs, and the patterns of dispersion were observed using an NIR imaging system. To compare retention times, fluorescence signals were evaluated in the stomach and small bowel of animals 1 week after injection.


RESULTS
A diluted concentration (~0.1 mg/ml) of ICG was optimal for NIR imaging compared with the conventional concentration (5 mg/ml) for visual inspection. When injected into the stomach, the signals of ICG and ICG/PGA complex were relatively large at the injection site, and signals were detected at multiple sentinel nodes and lymph nodes beyond them. The NIR-PNG signal intensity was relatively small at the injection site and limited to only one sentinel node with no additional node. When evaluated 1 week after injection, only the NIR-PNG signal was detected in the canine stomach, and the signal intensity at the lymph nodes of the porcine small bowel was the highest with NIR-PNG, followed by ICG/PGA complex and finally ICG.


CONCLUSIONS
NIR-PNG showed the best characteristics of less dispersion and longer retention in the sentinel nodes, and ICG/PGA complex remained longer than diluted ICG. These tracers could potentially be used as optimal tracers for sentinel node navigation surgery in gastric cancer.
Department of Surgery, Seoul National University Hospital, Seoul, Korea.
Seong-Ho
SH
Kong
Young-Woock
YW
Noh
Yun-Suhk
YS
Suh
Hye Sun
HS
Park
Hyuk-Joon
HJ
Lee
Keon Wook
KW
Kang
Hee Chan
HC
Kim
Yong Taik
YT
Lim
Han-Kwang
HK
Yang
D000818:Animals; D003952:Diagnostic Imaging / Q000379:methods*; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D005456:Fluorescent Dyes; D005936:Glucans; D007208:Indocyanine Green / Q000493:pharmacokinetics; D007422:Intestines / Q000187:drug effects; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis / Q000175:diagnosis; D008807:Mice, Inbred BALB C; D049329:Nanostructures; D011099:Polyglutamic Acid; D045663:Quantum Dots; D021701:Sentinel Lymph Node Biopsy / Q000379:methods*; D034421:Sus scrofa
D005456:Fluorescent Dyes; D005936:Glucans; D011099:Polyglutamic Acid; C009109:pullulan; D007208:Indocyanine Green