Optical Metabolic Imaging Identifies Breast Cancer Subtypes

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optical imaging breast cancer

Based on recent research, optical imaging technology, which measures metabolic activity in cancer cells, can precisely distinguish breast cancer subtypes and can detect responses to treatment as early as two days following therapy.

The study’s findings were published in the October issue of Cancer Research, a journal of the American Association for Cancer Research. 

 “The process of targeted drug development requires assays that measure drug target engagement and predict the response [or lack thereof] to treatment,” said graduate student in the department of biomedical engineering at Vanderbilt University (Nashville, TN, USA), Alex Walsh.

“We have shown that optical metabolic imaging [OMI] enables fast, sensitive, and accurate measurement of drug action. Importantly, OMI measurements can be made repeatedly over time in a live animal, which significantly reduces the cost of these preclinical studies.”

Human cells are subjected to wide chemical reactions known as metabolic activity to generate energy and this activity is modified in cancer cells. Cancer cells’ metabolic activity fluctuates when treated with anticancer drugs. OMI makes use of the fact that two molecules involved in cellular metabolism, called nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD), naturally give off fluorescence when exposed to particular forms of light. In this way, OMI produces characteristic signatures for cancer cells with a different metabolism and their responses to medications.

Walsh and colleagues used a custom-built, multiphoton microscope and attached it with a titanium-sapphire laser that causes NADH and FAD to emanate fluorescence. They applied specific filters to segregate the fluorescence emitted by these two molecules, and measured the ratio of the two as “redox ratio.”

When they placed normal and cancerous breast cells under the microscope, OMI produced noticable signals for the two types of cells. OMI could also distinguish between estrogen receptor-positive, estrogen receptor-negative, HER2-positive, and HER2-negative breast cancer cells.

The researchers then studied the effect of the anti-HER2 antibody trastuzumab on three breast cancer-cell lines that react differently to the antibody. They discovered that the redox ratios were considerably reduced in drug-sensitive cells after trastuzumab treatment, but unaffected in the resistant cells.

 They then grew human breast tumors in mice and treated some of these using trastuzumab. When they imaged the tumors in live mice, OMI showed a difference in response between trastuzumab-sensitive and -resistant tumors as early as two days following the first dose of the antibody.

 Fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging, in comparison, imaging, the standard clinical metabolic imaging modality, could not measure any conceivable difference in response between trastuzumab-sensitive and -resistant tumors at any time point throughout the research, which went on for a duration of 12 days.

According to the researchers, OMI can be utilized on newly removed tissues from patients; however, with additional refinements, it could be incorporated in endoscopes for live imaging of human cancers.

“Cancer drugs have profound effects on cellular energy production, and this can be harnessed by OMI to identify responding cells from nonresponding cells. We are hoping to develop a high-throughput screening method to predict the optimal drug treatment for a particular patient,” concluded Walsh.


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