Abstract
The complete removal of cancerous tissue is a central aim of surgical oncology, but is difficult to achieve in certain cases, especially when the removal of surrounding normal tissues must be minimized. Therefore, when post-operative pathology identifies residual tumor at the surgical margins, re-excision surgeries are often necessary. An intraoperative approach for tumor-margin assessment, insensitive to nonspecific sources of molecular probe accumulation and contrast, is presented employing kinetic-modeling analysis of dual-probe staining using surface-enhanced Raman scattering nanoparticles (SERS NPs). Human glioma (U251) and epidermoid (A431) tumors were implanted subcutaneously in six athymic mice. Fresh resected tissues were stained with an equimolar mixture of epidermal growth factor receptor (EGFR)-targeted and untargeted SERS NPs. The binding potential (BP; proportional to receptor concentration) of EGFR – a cell-surface receptor associated with cancer – was estimated from kinetic modeling of targeted and untargeted NP concentrations in response to serial rinsing. EGFR BPs in healthy, U251, and A431 tissues were 0.06 ± 0.14, 1.13 ± 0.40, and 2.23 ± 0.86, respectively, which agree with flow-cytometry measurements and published reports. The ability of this approach to quantify the BP of cell-surface biomarkers in fresh tissues opens up an accurate new approach to analyze tumor margins intraoperatively.
Highlights
Quantification of the binding potential of cell-surface receptors in fresh excised specimens via dual-probe modeling of SERS nanoparticles
Considering the high number of re-excision surgeries, there is a need for intraoperative methods of tumor-margin assessment such as wide-field imaging of the entire outer surface of a resected tissue
While wide-field imaging lacks the resolution of microscopic histopathology, it can provide a comprehensive image of the entire surgical margin surface and is unsusceptible to sampling errors introduced by selectively imaging thin sections of the tissue specimen at periodic intervals, as is done in conventional post-operative histopathology[11]
Summary
Quantification of the binding potential of cell-surface receptors in fresh excised specimens via dual-probe modeling of SERS nanoparticles. An intraoperative approach for tumor-margin assessment, insensitive to nonspecific sources of molecular probe accumulation and contrast, is presented employing kinetic-modeling analysis of dual-probe staining using surface-enhanced Raman scattering nanoparticles (SERS NPs). EGFR BPs in healthy, U251, and A431 tissues were 0.06 6 0.14, 1.13 6 0.40, and 2.23 6 0.86, respectively, which agree with flow-cytometry measurements and published reports The ability of this approach to quantify the BP of cell-surface biomarkers in fresh tissues opens up an accurate new approach to analyze tumor margins intraoperatively. Regardless of the margin criteria chosen, it is unequivocal that reexcision surgery is necessary in patients for whom tumor cells are identified at the surgical margin itself (i.e., the surface of the excised tissue) These re-excision procedures are time-consuming and add additional stress and risk for the patient. The first application of dual-probe kinetic modeling was carried out for topically applied SERS NP (surface-enhanced Raman scattering nanoparticle) molecular probes
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