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.
Highlights
An important step in the development and testing of new targeted cancer drug candidates is the acquisition of information about their pharmacological and pharmacodynamic action
Cetuximab-IRdye 800CW is used for single cell imaging, and pertuzumab-IRdye 800CW is used for the breast cancer model
We have demonstrated the potential of a multimodal microscopy combination of linear NIR fluorescence imaging with nonresonant four-wave mixing (NR-FWM) imaging to investigate the distribution of tumor-targeting drugs, such as cetuximab and pertuzumab, in cells and tissues
Summary
An important step in the development and testing of new targeted cancer drug candidates is the acquisition of information about their pharmacological and pharmacodynamic action. Targeted cancer drugs are designed to bind to specific biomolecules, involved in carcinogenesis and tumor growth, such as membrane proteins or ligands, for their effectiveness. To assess their effectiveness, the identification of target regions within a tumor with a high, subcellular resolution is a key aspect. Monoclonal antibodies (mAbs), such as cetuximab and trastuzumab, are currently used as targeted cancer drugs.[1] Cetuximab and trastuzumab are targeted to, respectively, the extracellular domain of human epidermal growth factor receptor (EGFR) and the human epidermal growth factor 2 (HER2) receptor at the cell membrane. Both EGFR and HER2 are implicated in regulating cell growth and proliferation and are frequently overexpressed, mutated, or dysregulated in certain cancer types. mAbs with their high affinity are suitable candidates for treatment, or when radioactively or fluorescently labeled, as tracer for tumors expressing these targets.[2,3,4]
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