Researchers from the The University of Texas at Austin and The University of Texas MD Anderson Cancer Center (both TX, USA) have developed a novel technique for the non-invasive screening of lymph nodes for metastatic cancer. The research, published recently in Cancer Research, enables early detection of cancer spread through non-invasive identification of micrometastases, providing a potential alternative to surgical biopsies.
The new method, currently tested in mice, uses ultrasound-guided photoacoustics combined with nanosensors to identify and target metastatic cells in lymph nodes.
Director of the NIBIB Program in Molecular Imaging, who funded the research, Richard Conroy, explained: “This work is an excellent example of the development of a cutting-edge technology that works very well in an experimental system but also has great potential to change the way we monitor and diagnose cancer metastasis. Identifying the accumulation of cells early in the process with some molecular characterization offers the opportunity for more targeted and effective treatment and fewer side effects.”
Sentinel lymph node biopsy is currently the standard in clinical practice for the identification of the regional spread of a tumor, however adverse effects such as swelling, pain, numbness and infection are observed in hundreds of thousands of cancer patients each year.
Several non-invasive imaging modalities have been developed to improve the accuracy and safety of lymph node biopsies, but at present these lack the specificity and sensitivity to replace invasive lymph node biopsy. Recognizing the shortcomings of these techniques, the researchers developed the current technology with the aim of achieving increased sensitivity, accuracy and specificity when compared to surgical biopsy.
Smart imaging probes that interact with metastatic cells are the main source of the increase in sensitivity and accuracy of the new method. Molecularly activated plasmonic nanosensors (MAPS), which include a gold nanoparticle that is seen by the imaging system, were developed by the researchers. The MAPS nanosensor also incorporates an antibody to EGFR. These two components enable the MAPS to locate the metastatic cell by using the antibody that binds to the EGFR receptor, which this is then visualized using photoacoustic imaging systems that detect the gold nanoparticle when the MAPS interact with a cancer cell.
An ultrasound-guided spectroscopic photoacoustic (sPA) imaging system was developed to detect the gold nanoparticles bound to metastatic cells in the lymph nodes. This system provides the high contrast and sensitivity of optical imaging and the resolution of ultrasound for tissues deep inside the body.
The new method was tested in a mouse model of oral cancer, where mice were injected with the EGFR-targeted MAPS and were subsequently imaged using sPA. It was demonstrated that the MAPS bound specifically to the metastatic cells in the lymph nodes close to the oral cavity tumor and the sPA imaging system enabled clear visualization.
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, equivalent to approximately 30 metastatic cells. This detection of such a small number of cells demonstrates the potential of the new method to facilitate the early identification of metastasis.
“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,” explained Stanislav Emelianov (The University of Texas at Austin).
Although currently tested in mice, the researchers are confident that the method could be translated into use in humans. However some alterations to the technology are required before this can occur; ultrasound frequencies that can penetrate to depths that would be needed in humans need to be identified and the potential toxicity of gold nanoparticles will have to be addressed. It is also hoped that the ability to identify specific abnormal cells early on could be used in other cancers, as well as conditions such as cardiovascular disease.