Clinical trial of combined radio- and fluorescence-guided sentinel lymph node biopsy in breast cancer

Abstract

Background Combining radioactive colloids and a near-infrared (NIR) fluorophore permit preoperative planning and intraoperative localization of deeply located sentinel lymph nodes (SLNs) with direct optical guidance by a single lymphatic tracer. The aim of this clinical trial was to evaluate and optimize a hybrid NIR fluorescence and radioactive tracer for SLN detection in breast cancer patients. Method Patients with breast cancer undergoing SLN biopsy were enrolled. The day before surgery, indocyanine green (ICG)-99mTc-Nanocolloid was injected periareolarly and a lymphoscintigram was acquired. Directly before surgery, blue dye was injected. Intraoperative SLN localization was performed by a gamma probe and the Mini-FLARETM NIR fluorescence imaging system. Patients were divided into two dose groups, with one group receiving twice the particle density of ICG and nanocolloid, but the same dose of radioactive 99mTechnetium. Results Thirty-two patients were enrolled in the trial. At least one SLN was identified pre- and intraoperatively. All 48 axillary SLNs could be detected by gamma tracing and NIR fluorescence imaging, but only 42 of them stained blue. NIR fluorescence permitted detection of lymphatic vessels draining to the SLN up to 29 hours after injection. Increasing the particle density by two-fold did not yield a difference in fluorescence intensity, median 255 (range 98 – 542) vs. median 284 (90 – 921; P = 0.590), or signal- to- background ratio, median 5.4 (range 3.0 – 15.4) vs. median 4.9 (3.5 – 16.3; P = 1.000), of the SLN. Conclusion The hybrid NIR fluorescence and radioactive tracer ICG-99mTc-Nanocolloid permitted accurate pre- and intraoperative detection of the SLNs in patients with breast cancer.

Fluorescence spectroscopy using indocyanine green for lymph node mapping

“…Lymph node mapping using NIR fluorescence provides a practical method with a high detection rate [9] while it circumvents the use of nuclear medicine which is available at a limited number of hospitals (about 4% of the total hospitals worldwide) [10,11]. However, the currently available NIR fluorescence imaging systems are bulky and lack spectroscopic and navigational features [6,7,12].…”

Near-infrared fluorescent probes in cancer imaging and therapy: an emerging field

“…All 48 axillary SLNs were found by radioactive tracer and NIRF dye. 165 In another study including 49 consecutive breast cancer patients, the use of ICG:HSA also provided additional benefits compared to RC alone. 166 In 32 women with vulvar cancer, 35 SLNs in 24 patients were intraoperatively detected by NIRF imaging using ICG:HSA and ICG alone, though no significant difference was found between them.…”

Multimodal imaging in radioguided surgery

“…5). The same hybrid tracer has now been used for SLN biopsy in various types of malignancies, e.g., melanoma and penile cancer [10,47,50]. This success should encourage further extension of the hybrid approach to surgical areas where there is room for improvement of the RGS technique.…”