Dataset Information

Fluorescence Polarization of Methylene Blue as a Quantitative Marker of Breast Cancer at the Cellular Level.

ABSTRACT: A quantitative technique to detect cancer in single cells could transform cancer diagnosis. Current cancer diagnosis utilizes histopathology, which requires tissue acquisition, extensive processing and, in most cases, relies on the qualitative morphological analysis of tissues and cells. Molecular biomarkers are only available for a few specific tumor subtypes. We discovered that the fluorescence polarization (Fpol) of Methylene Blue (MB) is significantly higher in cancer than in normal human breast tissues and cells. We confirmed that fluorescence polarization imaging did not affect the viability of the cells and yielded highly significant differences between cancer and normal cells using MB concentrations as low as 0.05 and 0.01 mg/ml. To explain this phenomenon we examined intracellular localization of MB and its fluorescence lifetime. We determined that higher fluorescence polarization of MB occurs due to its increased accumulation in mitochondria of cancer cells, as well as shorter fluorescence lifetime in cancer relative to normal cells. As quantitative MB Fpol imaging can be performed in vivo and in real time, it holds the potential to provide an accurate quantitative marker of cancer at the cellular level.

SUBMITTER: Yaroslavsky AN

PROVIDER: S-EPMC6353996 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Fluorescence Polarization of Methylene Blue as a Quantitative Marker of Breast Cancer at the Cellular Level.

Yaroslavsky Anna N AN Feng Xin X Muzikansky Alona A Hamblin Michael R MR

Scientific reports 20190130 1

A quantitative technique to detect cancer in single cells could transform cancer diagnosis. Current cancer diagnosis utilizes histopathology, which requires tissue acquisition, extensive processing and, in most cases, relies on the qualitative morphological analysis of tissues and cells. Molecular biomarkers are only available for a few specific tumor subtypes. We discovered that the fluorescence polarization (Fpol) of Methylene Blue (MB) is significantly higher in cancer than in normal human br ...[more]

PMID: 30700827

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Project description:Breast-conserving surgery is facing the challenge of objective tumor margin identification intraoperatively. Near-infrared fluorescence imaging would be an ideal approach to visualize tumor margins during surgeries. In this preliminary study, the feasibility of methylene blue-based near-infrared fluorescence imaging technique for breast cancer detection was assessed in resected human breast specimens after breast cancer surgeries. Thirty patients with breast cancer scheduled for surgical treatment were enrolled, including 10 patients with preoperative chemotherapy and 20 patients without. Each of them received an injection of 1 mg/kg methylene blue intravenously 3 hours before the surgery. Then, a home-developed methylene blue-specific near-infrared fluorescence imaging system was employed to image the resected breast tissues and identify the tumor by the fluorescence contrast. Specimens were taken for pathological examinations as the reference. There were no severe adverse events attributable to methylene blue. Of 20 patients, who did not receive preoperative chemotherapy, 16 exhibited fluorescent contrast on their resected tissues (signal-to-background ratio: 1.94 ± 0.71). In contrast, tumors were identified in 3 of 10 specimens from patients who underwent preoperative chemotherapy (signal-to-background ratio: 1.63 ± 0.38). A total of 35 tissues were sampled from 30 specimens. Besides 30 tumor samples, 5 more suspicious samples with fluorescence signal were confirmed to be benign hemorrhagic tissues. Therefore, a sensitivity of 0.63 and a positive predictive value of 0.79 were achieved by the methylene blue fluorescence imaging strategy. Here, we demonstrate the feasibility of using methylene blue fluorescence imaging to identify breast cancer. Preoperative chemotherapy had an impact on imaging effect, which may reduce the detection rate. After all, methylene blue fluorescence imaging has great potential to be used into breast-conserving surgery for tumor-positive margins detection, but further clinical trial study is needed ( http://www.chictr.org.cn/ Clinical Trial Registry ID: ChiCTR1800015400, Near-infrared fluorescence imaging applied in breast cancer identification with methylene blue).

Project description:BackgroundIndocyanine green (ICG) allows for the real-time visualization of lymphatic drainage and provides favorable performance for sentinel lymph node (SLN) mapping. However, the limited ability of tissue penetration of the near-infrared fluorescence of ICG may lead to the failure of lymph node detection in the traditional open approach of sentinel lymph node biopsy (SLNB) for breast cancer, especially in overweight or obese patients. To accurately and quickly detect SLNs, we applied fluorescence endoscopy with a dual-tracer method using ICG and methylene blue dye (MBD) in SLNB for breast cancer. We conducted this study to assess the feasibility and application value of this method in minimally invasive surgery.MethodsA total of 117 patients who received dual-tracer injection of ICG and MBD prior to endoscopic SLNB from November 2020 to September 2021 were examined in this study. The number of SLNs identified, the SLN identification rate, the time to identify the first SLN, the procedure duration, and the postoperative morbidity were analyzed.ResultsBiopsied SLNs could be identified in 116 patients (99.15%) with an average number of 5.12±1.87 per patient. Blue-stained SLNs were found in 99 patients (84.62%) and fluorescent SLNs in 112 patients (95.73%). A total of 34 patients (29.06%) had positive SLNs. In 6 cases (5.13%), the positive SLNs were only stained with ICG fluorescence. In 1 case (0.85%), the positive SLNs were only blue-stained with no fluorescence staining. The mean durations for the identification of the first SLN and endoscopic SLNB were 7.14±6.31 and 37.75±16.94 min, respectively. Upper-limb lymphoedema was observed 5 cases (4.27%) during a median follow-up period of 10 months.ConclusionsThe fluorescence endoscopy method assisted by dual tracer facilitates SLN detection with a comparatively short procedure duration and low complication rate. This approach could serve as a new method for SLNB for patients with breast cancer.

Dataset Information

Fluorescence Polarization of Methylene Blue as a Quantitative Marker of Breast Cancer at the Cellular Level.

Publications

Fluorescence Polarization of Methylene Blue as a Quantitative Marker of Breast Cancer at the Cellular Level.

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