Raman-Encoded Molecular Imaging with Topically Applied SERS Nanoparticles for Intraoperative Guidance of Lumpectomy

Abstract

Intraoperative identification of carcinoma at lumpectomy margins would enable reduced re-excision rates, which are currently as high as 20–50%. While imaging of disease-associated biomarkers can identify malignancies with high specificity, multiplexed imaging of such biomarkers is necessary to detect molecularly heterogeneous carcinomas with high sensitivity. We have developed a Raman-encoded molecular imaging (REMI) technique in which targeted nanoparticles are topically applied on excised tissues to enable rapid visualization of a multiplexed panel of cell surface biomarkers at surgical margin surfaces. A first-ever clinical study was performed in which 57 fresh specimens were imaged with REMI to simultaneously quantify the expression of four biomarkers HER2, ER, EGFR and CD44. Combined detection of these biomarkers enabled REMI to achieve 89.3% sensitivity and 92.1% specificity for the detection of breast carcinoma. These results highlight the sensitivity and specificity of REMI to detect biomarkers in freshly resected tissue, which has the potential to reduce the rate of re-excision procedures in cancer patients.

Review of methods for intraoperative margin detection for breast conserving surgery

“…This imaging method is only applicable to the tissue surface, thus, it is not able to tell if margins are clear 2 mm below the surface for DCIS. 114 REMI is attractive as a technology for use in identifying positive margins since it gives relevant biological information in these biomarkers. It does suffer from the need for use of applied nanoparticles and long scan times.…”

A reflection on noninvasive molecular imaging of cancer spread to lymph nodes

“…However, no single or "perfect" tumor-specific marker has been identified that would be overexpressed by all cancer types, although it is possible to combine multiple biomolecule vectors (target markers) 4 or multiple imaging agents. 5…”

Real-time Visualization of Breast Carcinoma in Pathology Specimens From Patients Receiving Fluorescent Tumor-Marking Agent Tozuleristide

“…12,13 Rates of reexcision vary but it is reported that between 20% and 50% of patients undergo additional surgery when final surgical resection pathology demonstrates positive or close margins. 14,15 To reduce the need to return to the operating room, a number of ex vivo imaging techniques including surface enhanced Raman scattering nanoparticles 16,17 and intrinsic Raman spectroscopy, [18][19][20] optical coherence tomography, 21,22 and confocal 23 and light reflectance spectroscopy 24,25 have been explored for their intraoperative use in breast margin assessment. These techniques have been developed to image the tissue at margin in real time with the hope of detecting tumor present adjacent to margin during surgery.…”