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Document type:
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Author(s):
Rotter, Lara K; Berisha, Naxhije; Hsu, Hsiao-Ting; Burns, Kathleen H; Andreou, Chrysafis; Kircher, Moritz F
Title:
Visualizing surface marker expression and intratumoral heterogeneity with SERRS-NPs imaging.
Abstract:
Cell surface marker expression in tumors dictates the selection of therapeutics, therapy response, and survival. However, biopsies are invasive, sample only a small area of the tumor landscape and may miss significant areas of heterogeneous expression. Here, we investigated the potential of antibody-conjugated surface-enhanced resonance Raman scattering nanoparticles (SERRS-NPs) to depict and quantify high and low tumoral surface marker expression, focusing on the surface markers epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) in an intracerebral and peripheral setting with an inter- and intratumoral comparison of Raman signal intensities. Methods: ICR-Prkdc mice were injected with glioblastoma, epidermoid carcinoma, or breast tumor cell lines intracerebrally and peripherally. SERRS-NPs were functionalized with cetuximab or trastuzumab and administered via tail vein injection. Raman imaging was performed 18 hours post-injection in excised tumors and in vivo through the skull. Tumors were then fixed and processed for immunohistochemical evaluation. Results: Confirmed by MRI and immunohistochemistry for EGFR and HER2, our results demonstrate that antibody-conjugated SERRS-NPs go beyond the delineation of a tumor and offer clear and distinct Raman spectra that reflect the distribution of the targeted surface marker. The intensity of the SERRS-NP signal accurately discriminated high- versus low-expressing surface markers between tumors, and between different areas within tumors. Conclusion: Biopsies can be highly invasive procedures and provide a limited sample of molecular expression within a tumor. Our nanoparticle-based Raman imaging approach offers the potential to provide non-invasive and more comprehensive molecular imaging and an alternative to the current clinical gold standard of immunohistochemistry.
Journal title abbreviation:
Nanotheranostics
Year:
2022
Journal volume:
6
Journal issue:
3
Pages contribution:
256-269
Fulltext / DOI:
doi:10.7150/ntno.67362
Pubmed ID:
http://view.ncbi.nlm.nih.gov/pubmed/35145836
TUM Institution:
Professur für Neuroradiologie (Prof. Zimmer)
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