Sentinel lymph node biopsy revisited: Ultrasound-guided photoacoustic detection of micrometastases using molecularly targeted plasmonic nanosensors

Abstract

Metastases rather than primary tumors are responsible for killing most patients with cancer. Cancer cells often invade regional lymph nodes (LN) before colonizing other parts of the body. However, due to the low sensitivity and specificity of current imaging methods to detect localized nodal spread, an invasive surgical procedure-sentinel LN biopsy-is generally used to identify metastatic cancer cells. Here, we introduce a new approach for more sensitive in vivo detection of LN micrometastases, based on the use of ultrasound-guided spectroscopic photoacoustic (sPA) imaging of molecularly activated plasmonic nanosensors (MAPS). Using a metastatic murine model of oral squamous cell carcinoma, we showed that MAPS targeted to the epidermal growth factor receptor shifted their optical absorption spectrum to the red-near-infrared region after specific interactions with nodal metastatic cells, enabling their noninvasive detection by sPA Notably, LN metastases as small as 50 (J,m were detected at centimeter-depth range with high sensitivity and specificity. Large sPA signals appeared in metastatic LN within 30 minutes of MAPS injection, in support of the clinical utility of this method. Our findings offer a rapid and effective tool to noninvasively identify micrometastases as an alternate to sentinal node biopsy analysis.