Methylene Blue Near-Infrared Fluorescence Imaging in Breast Cancer Sentinel Node Biopsy
by
, , , ,
Oliver Budner
1, 
Tomasz Cwalinski
2,
Jarosław Skokowski
2,3,4
,
Luigi Marano
5
,
Luca Resca
5,
Natalia Cwalina
6,
Leszek Kalinowski
3,4,7, 
Richelle Hoveling
8,
Franco Roviello
5 and
Karol Polom
2,* 1
Frauenheilkunde und Geburtshilfe, HELIOS Kliniken Schwerin, Wissmarsche Street 393-397, 19-055 Schwerin, Germany
2
Department of Surgical Oncology, Faculty of Medicine, Medical University of Gdansk, Marii Sklodowskiej-Curie Street 3a, 80-217 Gdansk, Poland
3
Department of Medical Laboratory Diagnostics–Biobank Fahrenheit BBMRI.pl, Medical University of Gdansk, Debinki Street 7, 80-211 Gdańsk, Poland
4
Biobanking and Biomolecular Resources Research Infrastructure Poland (BBMRI.pl), 80-210 Gdańsk, Poland
5
Department of Medicine, Surgery and Neurosciences, Unit of General Surgery and Surgical Oncology, University of Siena, Viale Bracci 16, 53-100 Siena, Italy
6
Department of Pediatrics Ascension, St. John Children’s Hospital, Detroit, MI 48236, USA
7
BioTechMed/Department of Mechanics of Materials and Structures, Gdansk University of Technology, Gabriela Narutowicza Street 11/12, 80-233 Gdansk, Poland
8
Quest Medical Imagining, Industrieweg 41, 1775 PW Middenmeer, The Netherlands
*
Author to whom correspondence should be addressed.
Cancers 2022, 14(7), 1817; https://doi.org/10.3390/cancers14071817
Submission received: 14 March 2022
/
Accepted: 31 March 2022
/
Published: 3 April 2022
(This article belongs to the Topic Biomedical Photonics)
Simple Summary
Currently the gold standard for sentinel node biopsy in breast cancer patients is radioactive nanocolloid and a blue dye. In the age of fluorescence guided surgery new fluorophores are used and methylene blue presents some fluorescent properties. This study is the first in a clinical series presenting the possible use of methylene blue as a fluorescent dye for the identification of sentinel nodes in breast cancer sentinel node biopsy. We presented a feasibility of this new method and also in additional experiments because of the quenching effect limitation, found possible dilution of methylene blue presenting improved fluorescence.
Abstract
Introduction: 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. Material and methods: 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. Results: 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). Conclusions: 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.
Keywords:
breast cancer; methylene blue; sentinel node biopsy; fluorescence
