Page 43 - Fluorescence-guided cancer surgery

Detection of breast cancer using methylene blue 41
INTRODUCTION
Breast cancer is the most common malignancy in women worldwide and is a leading cause of cancer-related mortality1. More than 1.2 million cases are diagnosed every year, a ecting 10–12% of the female population and accounting for 500,000 deaths per year worldwide.
In early breast cancer, breast conserving surgery (BCS) is the preferred standard of care. Despite preoperative imaging modalities such as CT and MRI, intraoperative identi cation of breast cancer tissue can be challenging. Previous studies reported that the incidence of tumor cells at or near the cut edge of the surgical specimen ranged from 5% to 82%, with the majority of studies indicating positive resection margins in 20%–40% of patients after resection of the primary tumor2. Positive margins may lead to additional surgical procedures, delays in adjuvant treatment, increased morbidity, poor aesthetic results, and increased healthcare costs. Therefore, there is an urgent need for new technology to identify breast cancer tissue intraoperatively.
Technetium(99mTc)-sestamibi (MIBI) is a lipophilic cation used for preoperative, non-invasive identi cation of malignant tissue via SPECT imaging3. Using 99mTc-MIBI, preoperative identi cation of breast cancer is possible in approximately 83-90% of patients3-5. Based on the lipophilic, cationic structure of Methylene Blue (MB), and the fact that like 99mTc-MIBI, MB can function as a perfusion tracer in vivo6;7, we hypothesized that it too might be able to detect breast tumors. Importantly, MB is a clinically available tracer that can be used at relatively low dose (0.5-1 mg/kg) as a uorescent tracer during NIR uorescence imaging. NIR uorescence imaging is a promising technique to assist in the intraoperative identi cation of sentinel lymph nodes, tumors, and vital structures8.
During 99mTc-MIBI SPECT imaging, early (within 30 min after tracer administration) and delayed (3 h post tracer administration) imaging is performed in succession5;9. The reason for this is to di erentiate more accurately between malignant and benign lesions because it is presumed that tracer uptake in malignant lesions might persist, whereas clearance from benign lesions would be more rapid. Delayed imaging could thereby result in higher tumor-to-background ratios (TBRs) from lower background signal.
The aim of this study was to determine the feasibility of using MB as an NIR uorescent tracer for the identi cation of breast tumor intraoperatively, and to compare early and delayed imaging protocols.