Imaging technique identifies early metastasis in lymph nodes

A highly sensitive and accurate imaging technique for noninvasive screening of lymph nodes for metastatic cancer has been developed. This new technique uses an imaging approach known as ultrasound-guided photoacoustics combined with nanosensors designed to target and identify metastatic cells in lymph nodes. The initial study, done in mice, was published in Cancer Research (2015; doi:10.1158/0008-5472).

More than 90% of cancer deaths can be attributed to metastases either directly or indirectly. Currently, sentinel lymph node (SLN) biopsy, an invasive surgical procedure, is used to identify the regional spread of tumor. This procedure results in adverse effects including swelling, pain, numbness, and risk of infection in hundreds of thousands of cancer patients per year.

In efforts to improve the accuracy and safety of lymph node biopsies, a number of noninvasive imaging modalities have been tested in animals and patients. Knowing the shortcomings of previous attempts to use noninvasive imaging techniques, the researchers at the University of Texas at Austin and the University of Texas MD Anderson Cancer Center in Houston developed a technology that is noninvasive and may have better sensitivity, accuracy, and specificity than surgical biopsy.

The group built a molecularly activated plasmonic nanosensor (MAPS) to work as a smart imaging probe to interact with the metastatic cells. The MAPS components include a gold nanoparticle, which is the part of the nanosensor seen by the imaging system. The MAPS nanosensor also contains an antibody to the epidermal growth factor receptor (EGFR). This antibody was chosen because EGFR is abnormally highly expressed on the surface of many cancers.

With these two components, the MAPS can find the metastatic cell using the antibody that binds to the EGFR receptor. It can be seen using photoacoustic imaging systems that detect the gold nanoparticle, but only when the MAPS interacts with a cancer cell.

To detect the gold nanoparticles bound to metastatic cells in the lymph nodes, the researchers developed an ultrasound-guided spectroscopic photoacoustic (sPA) imaging system. The technology provides the high contrast and sensitivity of optical imaging with the ability of ultrasound to provide clear resolution even in tissues deep inside the body.

Overall, tumor-bearing mice injected with the EGFR-targeted MAPS showed a sensitivity of 100% and a specificity of 87% for detection of lymph node micrometastases as small as 50 micrometers, which corresponds to about 30 metastatic cells. The detection of such a small number of cells in the lymph node offers a system that has the ability to identify metastasis very early in the process, which would allow early treatment.

“This combination greatly improves sensitivity and specificity of detection of cancerous cells in lymph nodes as compared to any other imaging modality in use today,” said co-senior author Konstantin Sokolov, PhD, of MD Anderson.

“Our method has a great potential to provide dramatic improvement in the clinical staging, prognosis, and therapeutic planning for cancer patients with metastatic disease without the need for invasive surgical biopsy,” added co-senior author Stanislav Emelianov, PhD.

The study was funded by the National Institutes of Health through the National Institute of Biomedical Imaging and Bioengineering (NIBIB) grant number R01EB008101 and the National Cancer Institute.

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