Abstract
We assessed the use of ultrasound (US)-guided photoacoustic imaging (PAI) and anti-EGFR antibody-conjugated gold nanorods (anti-EGFR-GNs) to non-invasively detect EGFR-expressing primary tumor masses and regional lymph node (LN) metastases in breast tumor mice generated by injecting MCF-7 (EGFR-negative) or MDA-MB-231 (EGFR-positive) human breast cells using a preclinical Vevo 2100 LAZR Imaging system. Anti-EGFR-GNs provided a significant enhancement in the PA signal in MDA-MB-231 tumor and the axillary LN metastases relative to MCF-7 tumor and non-LN metastases. We demonstrated that US-guided PAI using anti-EGFR-GNs is highly sensitive for the selective visualization of EGFR-expressing breast primary tumors as well as LN micrometastases.
Highlights
Breast cancer is a heterogeneous disease comprising several biologically distinct subtypes, and the majority of breast cancer-related deaths are mainly due to incurable metastatic diseases [1]
The PA signal measured from the axillary lymph node (LN) just before the injection was similar to that 24 h after the injection of ICG
Photoacoustic imaging (PAI) using various exogenous contrast agents is a rapidly emerging non-ionizing and noninvasive imaging technology that integrates the merits of strong optical contrast with high spatial resolution to image the course and flow of lymphatic vessels as well as to selectively detect breast tumors, including metastases [5,6,7,8]
Summary
Breast cancer is a heterogeneous disease comprising several biologically distinct subtypes, and the majority of breast cancer-related deaths are mainly due to incurable metastatic diseases [1]. Targeting the epidermal growth factor receptor (EGFR) has been proposed as a promising imaging biomarker for selective detection and treatment of EGFR-positive TNBC including metastases, but it is still in the early stages [2,3,4]. Gold nanorods (GNs) with distinctive rod shapedependent optical properties have been proposed as attractive antibody-conjugated PA contrast agents to enable the selective detection of primary tumors and metastases in vivo [11,12,13], yet the study of in vivo US-guided PAI using molecular targeted GNs to more sensitively and target and identify primary tumor as well as a small number of metastatic cancer cells in regional LN in breast cancer models is still its infancy
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