An optical imaging technique that measures metabolic activity in cancer cells can identify breast cancer subtypes and reveal treatment response as soon as two days post-therapy administration, according to a study published Oct. 15 in the American Association for Cancer Research’s journal, Cancer Research.
Alteration of metabolic activity in human cells is a common indication of cancer, and drugs that are often used to treat cancerous cells change this activity. Optical metabolic imaging (OMI) capitalizes on a unique characteristic of two metabolic coenzymes: nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD). These molecules inherently emanate fluorescence when in contact with certain forms of light, so OMI exposes NADH and FAD to light in order to produce signatures for cancer cells with varying metabolism and assess their subsequent responses to drugs. OMI, in comparison with other current preclinical and clinical methods that assess metabolic state in tumors, is a quantitative, non-invasive, and high-resolution tool, according to Alex Walsh, a graduate student of Vanderbilt University’s Department of Biomedical Engineering, and colleagues.
In the study, Walsh and colleagues first utilized a multiphoton fluorescence microscope and titanium-sapphire laser to emit fluorescence from NADH and FAD. Specific filters isolated the fluorescence and measured the “optical redox ratio” of the two, which allowed for a dynamic measure of cellular metabolism. Upon placing healthy and cancerous breast cells under the microscope, the researchers discovered that OMI made distinct signals for two types of cells. The imaging technique also distinguished between estrogen receptor-positive, estrogen receptor-negative, HER2-positive, and HER2-negative breast cancer cells.
Once they established OMI’s ability to determine breast cancer subtypes, the researchers tested the effect of tastuzumab, the anti-HER2 antibody, on three breast cancer cell lines that respectively respond differently to the antibody. After tastuzumab treatment, redox ratios significantly decreased in drug-sensitive cells but remained unchanged in resistant cells.
Lastly, Walsh and colleagues grew human breast tumors in mice, of whom a portion were treated with the antibody. When the tumors were imaged, OMI revealed a marked difference in response between trastuzumab-sensitive and –resistant tumors as soon as two days after the first dosage of the antibody was given. FDG-PET imaging, one of the current methods used to assess metabolic state in tumors, did not measure any difference between the two types of tumors at any point during the 12 day experiment.
“Our results have significant implications for rapid assessment of drug action in preclinical models, which would greatly accelerate drug development studies,” wrote Walsh and colleagues.
Currently, optical metabolic imaging can be used on tissues freshly excised from patients. However, with further development, the technique could be incorporated into endoscopes for live imaging of human cancers and other diseases.
“These methodologies are potentially broadly applicable outside the cancer and imaging communities, including those in drug development and metabolism research across multiple diseases,” wrote the authors. “Although we see OMI as an immediately powerful tool in preclinical models, it also may directly impact patient care as an adjunct to current practice.”