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

Abstract

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-c-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. Conclusion 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.

Optimal settings and accuracy of indocyanine green fluorescence imaging for sentinel node biopsy in early gastric cancer

“…However, secondary node contamination is problematic, as true SNs are difficult to distinguish from secondary nodes. Novel fluorescence agents have already been developed that have fluorescence and colloid particle characteristics (35)(36)(37)(38)(39). These novel agents would only detect fluorescent SNs and not secondary nodes, and therefore, would be the most potentially useful for conducting a laparoscopic SN biopsy in gastric cancer.…”

Biochemical and molecular characterization of a new pullulan producer Rhodosporidium paludigenum PUPY-06

“…Biomedical applications of pullulan include drug delivery, gene delivery [21,22], tissue engineering [23], vaccination [24,25], medical imaging [26], plasma expander [27], molecular chaperones [28], and film forming [29].…”

Advances in the application of nanotechnology in the diagnosis and treatment of gastrointestinal tumors

“…Kong et al (70) found that IRDye900-conjugated pullulan-cholesterol nanoprobe NIR-PNG exhibited the favorable characteristics of lower dispersion and longer retention in the SLN compared to diluted indocyanine green (ICG) and ICG/poly-γ-glutamic acid complex following injection into the stomachs of dogs and pigs (70). Nanogels may be controlled for various applications in drug delivery and may be tailored to exhibit exceptional stability, low cytotoxicity and higher blood compatibility (71,72).…”