Nano‐sized fluorescent particles as new tracers for sentinel node detection: Experimental model for decision of appropriate size and wavelength

Abstract

The concepts of made-to-order and low-invasiveness medicines are becoming widely accepted. A treatment for cancer, with minimum invasive surgery and without lymph nodes dissection based on sentinel lymph node (SN) navigation surgery, would adhere to these concepts. Dyes and/or radioisotopes are employed for SN detection in standard methods, however, each detection method has advantages and disadvantages. To make up for the disadvantages, we aimed at developing a new non-invasive method using fluorescent beads of uniform nano-size that could efficiently visualize SN from outside the body, and conducted experiments to determine the appropriate size and fluorescent wavelength. We examined various bead sizes and fluorescent wavelengths. The sizes were 20, 40, 100 and 200 nm. The fluorescent peak wavelengths of the beads were yellow-green (515 nm), dark red (680 nm), far red (720 nm) and infrared (755 nm). The beads were subcutaneously injected into the foot pad of the hind leg of a rat, and followed by laser scanning of the inguinal area for fluorescence observation. T he sentinel node (SN) is the first lymph node on the lymphatic drainage pathway from the cancerous tumor. In cases where the SN has a metastasis, there is the possibility of another positive node. When the SN is negative for metastasis, we can consider that there will be no other positive node and lymph node dissection (LND) is not necessary except for of the SN. This leads to the avoidance of functional or organic complication after LND. Preventive and systematic LND in cancer surgery has been accepted as a standard technique for over 100 years, however, the modern concept of minimizing the invasiveness of medical treatment is changing surgical procedures. This SN navigation surgery presents a new choice to patients as a made-to-order medical treatment. There are two major methods for detection of SN using tracer molecules: (i) a dye method in which iso-sulfan blue is used; and (ii) a radioisotope (RI) method in which 99m Tc with phytic acid is used. They are subcutaneously injected at the periphery of the tumor, and then the SN can be identified through tracer accumulation.(1-4) High sensitivity in the detection of an SN can be achieved using these two methods together. However, there are disadvantages for each method. The dye method requires some great skill, and cannot be detected without a skin incision. The RI method requires radioactive agents it, therefore, can only be performed at certain hospitals because of the regulations for handling these.To make up for the disadvantages, we designed fluorescent nano-sized beads as a new alternative tracer. There are many factors that might influence their movement in the lymphatic system when particles are subcutaneously administered in vivo. We noted the particle size as the most important factor. Small sized particles immediately move into lymphatic capillaries and pass through the interstices of the endothelial cells from the interstitial tissue. Large-sized particles are carried by macrophages after...

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