Hybrid imaging of fluorescently labeled cancer drugs and label-free four-wave mixing microscopy of cancer cells and tissues

Abstract. Fluorescent labels are well suited as tracers for cancer drug monitoring. Identifying cellular target regions of these drugs with a high resolution is important to assess the working principle of a drug. We investigate the applications of label-free nonresonant four-wave mixing (NR-FWM) microscopy in biological imaging in combination with fluorescence imaging of fluorescently labeled cancer drugs. Results from human A431 tumor cells with stained nuclei and incubated with IRdye 800CW labeled cancer drug cetuximab targeting epidermal growth factor receptor at the cell membrane show that NR-FWM is well suited for cellular imaging. A comparison of vibrationally nonresonant FWM imaging with vibrational resonant coherent anti-Stokes Raman scattering signals revealed nearly identical qualitative information in cellular imaging. NR-FWM is also suitable for tumor tissue imaging in combination with fluorescence imaging of IRdye 800CW labeled, human epidermal growth factor 2 targeting cancer drug pertuzumab and provides additional information over transmission microscopy.

[1]  A. Heikal.  Intracellular coenzymes as natural biomarkers for metabolic activities and mitochondrial anomalies. , 2010, Biomarkers in medicine.

[2]  Feruz Ganikhanov,et al.  High-sensitivity vibrational imaging with frequency modulation coherent anti-Stokes Raman scattering (FM CARS) microscopy. , 2006, Optics letters.

[3]  Jane A Dickerson,et al.  Current Applications of Liquid Chromatography / Mass Spectrometry in Pharmaceutical Discovery After a Decade of Innovation , 2008 .

[4]  Alastair H Kyle,et al.  Direct Visualization of Heterogeneous Extravascular Distribution of Trastuzumab in Human Epidermal Growth Factor Receptor Type 2 Overexpressing Xenografts , 2008, Clinical Cancer Research.

[5]  Y. Yarden,et al.  Untangling the ErbB signalling network , 2001, Nature Reviews Molecular Cell Biology.

[6]  Conor L Evans,et al.  Heterodyne coherent anti-Stokes Raman scattering (CARS) imaging. , 2006, Optics letters.

[7]  Maike Windbergs,et al.  Pharmaceutical applications of non-linear imaging. , 2011, International journal of pharmaceutics.

[8]  Alistair Elfick,et al.  Nonlinear optical microscopy for drug delivery monitoring and cancer tissue imaging , 2010 .

[9]  Wei Min,et al.  Near-degenerate four-wave-mixing microscopy. , 2009, Nano letters.

[10]  Ian F Tannock,et al.  The distribution of the therapeutic monoclonal antibodies cetuximab and trastuzumab within solid tumors , 2010, BMC Cancer.

[11]  Louise Duloquin,et al.  Combined third-harmonic generation and four-wave mixing microscopy of tissues and embryos , 2011, Biomedical optics express.

[12]  Yosef Yarden,et al.  Biology of HER2 and Its Importance in Breast Cancer , 2001, Oncology.

[13]  Wolfgang Werner Langbein,et al.  Four-wave mixing of gold nanoparticles for three-dimensional cell microscopy , 2009 .

[14]  Ji-Xin Cheng,et al.  Shedding new light on lipid biology with coherent anti-Stokes Raman scattering microscopy , 2010, Journal of Lipid Research.

[15]  Eva M. Sevick-Muraca,et al.  Single-Dose Intravenous Toxicity Study of IRDye 800CW in Sprague-Dawley Rats , 2010, Molecular Imaging and Biology.

[16]  X. Xie,et al.  Polarization coherent anti-Stokes Raman scattering microscopy. , 2001, Optics letters.

[17]  Pierre O. Bagnaninchi,et al.  Multimodal, label‐free nonlinear optical imaging for applications in biology and biomedical science , 2013 .

[18]  R. Anderson,et al.  The optics of human skin. , 1981, The Journal of investigative dermatology.

[19]  W Wang,et al.  Monoclonal Antibody Pharmacokinetics and Pharmacodynamics , 2008, Clinical pharmacology and therapeutics.

[20]  S. A. Akhmanov,et al.  Coherent ellipsometry of Raman scattering of light , 1977 .

[21]  Marina Marjanovic,et al.  Longitudinal Label-free Tracking of Cell Death Dynamics in Living Engineered Human Skin Tissue with a Multimodal Microscope References and Links , 2022 .

[22]  Satoshi Kawata,et al.  Imaging of EdU, an alkyne-tagged cell proliferation probe, by Raman microscopy. , 2011, Journal of the American Chemical Society.

[23]  Jan Greve,et al.  Design, optimization, and characterization of a narrow-bandwidth optical parametric oscillator , 1999 .

[24]  Vasilis Ntziachristos,et al.  Intraoperative Near-Infrared Fluorescence Tumor Imaging with Vascular Endothelial Growth Factor and Human Epidermal Growth Factor Receptor 2 Targeting Antibodies , 2011, The Journal of Nuclear Medicine.

[25]  Hyesung Jeon,et al.  In vivo fluorescence imaging for cancer diagnosis using receptor-targeted epidermal growth factor-based nanoprobe. , 2013, Biomaterials.

[26]  Shi Ke,et al.  In vivo fluorescent optical imaging of cytotoxic T lymphocyte migration using IRDye800CW near-infrared dye. , 2008, Applied optics.

[27]  Cees Otto,et al.  Noninvasive imaging of protein metabolic labeling in single human cells using stable isotopes and Raman microscopy. , 2008, Analytical chemistry.