Detection of sentinel nodes by a novel red‐fluorescent dye, ATX‐S10Na (II), in an orthotopic xenograft rat model of human gastric carcinoma

Abstract

Background and Objective: We developed a new imaging system to detect sentinel nodes (SNs) using a novel fluorescent tracer, ATX-S10Na(II), and investigated its usefulness in an animal model. Study Design/Materials and Methods: Human gastric carcinoma cells were implanted orthotopically into nude rats. ATX-S10Na(II) was injected subserosally into the primary tumor lesion, and visualized by a fluorescence spectro-laparoscope. Presence of tumor cells in lymph nodes (LNs) was determined by RT-PCR specific for human b-actin. Results: Injection of ATX-S10Na(II) was successful in 27 tumor-bearing rats. A red fluorescence was incorporated into the left gastric and hepatic LNs in 25 and 2 rats, respectively. Of note, human b-actin was detected in most of these LNs. Fluorescence was not detected in LNs that did not contain cancer. Conclusion: ATX-S10Na(II) is useful for the detection of cancer-containing SNs in an animal model of gastric carcinoma, and may serve as a novel tracer in SN navigation surgery.

Novel Biomedical Imaging Approach for Detection of Sentinel Nodes in an Orthotopic Xenograft Rat Model of Human Gastric Carcinoma

“…7, however, ATX-S10Na (II) is incorporated rapidly into lymphatic tissues after subserosal injection into the primary tumor. Our study confirmed for the first time that ATX-S10Na (II) is taken up by local lymphatic tissues when it is subserosally injected into the primary tumor lesion (Koyama et al, 2007a). One possible explanation for the phenomenon is that the chemical structure of ATX-S10Na (II) is water-soluble, but not lipidsoluble (Matsumoto et al, 2003;Mori et al, 2000aMori et al, , 2000bNakajima et al, 1992Nakajima et al, , 1998.…”

“…No obvious toxicity was observed in rats that were injected locally with ATX-S10Na (II) at a dose of 1.3-2.5 mg/kg in our study (Koyama et al, 2007a). This dosage is much smaller than that of systemic administration given intravenously at a dose of 5-25 mg/kg, which caused little, if any, toxicity in vivo (Matsumoto et al, 2003;Mori et al, 2000a;Nakajima et al, 1992Nakajima et al, , 1998.…”

“…In addition, ATX-S10Na (II) has a high affinity and specificity for tumor tissues, and thereby selectively accumulates in tumor tissues (Matsumoto et al, 2003;Mori et al, 2000aMori et al, , 2000bNakajima et al, 1992Nakajima et al, , 1998. To our knowledge, our study was the first report that describes the use of a hydrophilic photosensitizer, ATX-S10Na (II), for the detection of SNs in orthotopic transplants of human gastric carcinoma (Koyama et al, 2007a). In the present chapter, we showed a novel fluorescence-guided imaging system to detect SNs using a photosensitizing agent, ATX-S10Na (II), as a novel fluorescent tracer, and its usefulness for a fluorescence-guided lymphatic mapping system in an animal model of human gastric carcinoma.…”

“…Therefore, it has substantially less adverse effects (Matsumoto et al, 2003;Mori et al, 2000a;Nakajima et al, 1992;Nakajima et al, 1998). We acknowledge that our studies were conducted in an orthotopic xenograft rat model (Koyama et al, 2007a(Koyama et al, , 2007b, in which the structure and anatomy of the regional lymphatic network may be different from those of human system (Ichikura et al, 2002;Miwa et al, 2003). Alternatively, the rat model may not be comparable to early gastric carcinoma in humans, for which sentinel node navigation surgery is more suitable (Hiratsuka et al, 2001;Isozaki et al, 2004).…”

Systematic Review of Studies Investigating Sentinel Node Navigation Surgery and Lymphatic Mapping for Gastric Cancer

“…39,41,43,50,56 All the studies were designed as prospective trials. Of these, 37 (80%) were prospective descriptive trials, whereas 9 (20%) intentionally planned to include comparative groups.…”