Methylene Blue Near-Infrared Fluorescence Imaging in Breast Cancer Sentinel Node Biopsy

Fluorescence-based navigation for breast cancer sentinel node biopsy is a novel method that uses indocyanine green as a fluorophore. However, methylene blue (MB) also has some fluorescent properties. This study is the first in a clinical series presenting the possible use of MB as a fluorescent dye for the identification of sentinel nodes in breast sentinel node biopsy.

Forty-nine patients with breast cancer who underwent sentinel node biopsy procedures were enrolled in the study. All patients underwent standard simultaneous injection of nanocolloid and MB. We visualized and assessed the sentinel nodes and the lymphatic channels transcutaneously, with and without fluorescence, and calculated the signal-to-background ratio (SBR). We also analyzed the corresponding fluorescence intensity of various dilutions of MB.

In twenty-three patients (46.9%), the location of the sentinel node, or the end of the lymphatic path, was visible transcutaneously. The median SBR for transcutaneous sentinel node location was 1.69 (range 1.66-4.35). Lymphatic channels were visible under fluorescence in 14 patients (28.6%) prior to visualization by the naked eye, with an average SBR of 2.01 (range 1.14-5.6). The sentinel node was visible under fluorescence in 25 patients (51%). The median SBR for sentinel node visualization with MB fluorescence was 2.54 (range 1.34-6.86). Sentinel nodes were visualized faster under fluorescence during sentinel node preparation. Factors associated with the rate of visualization included diabetes (p = 0.001), neoadjuvant chemotherapy (p = 0.003), and multifocality (p = 0.004). The best fluorescence was obtained using 40 μM (0.0128 mg/mL) MB, but we also observed a clinically relevant dilution range between 20 μM (0.0064 mg/mL) and 100 μM (0.032 mg/mL).

For the first time, we propose the clinical usage of MB as a fluorophore for fluorescence-guided sentinel node biopsy in breast cancer patients. The quenching effect of the dye may be the reason for its poor detection rate. Our analysis of different concentrations of MB suggests a need for a detailed clinical analysis to highlight the practical usefulness of the dye.