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• W2333178407 abstract "To demonstrate in vitro in vivo epidermal growth factor receptor (EGFR) targeting specificity of a multifunctional molecular probe by combining the receptor-targeting monoclonal antibody (mAb) with the contrast agent Gadolinium (Gd). The molecular probe was comprised of two functional subunits, anti-EGFR antibodies for tumor targeting and dendrimer nanoclusters (DNCs) loaded with Gd for MR image contrast. Gd was tethered to the DNCs by Diethylene Triamine Pentaacetic Acid (DTPA) anhydride in alkaline condition. Avidin, a tetrameric biotin-binding protein, was added to biotinylated anti-EGFR mAb (C225) and biotinylated Gd-DNC, producing the multifunctional probe. The probe was tested for its targeting specificity in vitro and in vivo. The target (human head and neck cancer 15B) and the control HEK293 cells were cultured and the probe was mixed with the fixed cells to allow target-probe binding, followed by multiple PBS washes to remove any unbound probe. Flow cytometry and MR imaging were performed to verify cell targeting and reduction in T1 relaxation times, respectively. The shift in fluorescent intensity (SFI) was used to determine the relative EGFR expression level and the cell targeting ability of the probe. T1 relaxation times as a function of different probe concentrations were determined by an inversion recovery fast spin echo imaging sequence on a 3T MR system at 25oC with the following settings: TE = 12ms, TR = 6000ms, inversion time, TI = 40-2800ms. Binding specificity of the probe in vivo was tested in the nude mice who were implanted with 15B xenografts and imaged under MR to observe region-of-interest specific uptake following injection of the probe via the tail vein. Flow cytometry data revealed high targeted binding affinity of the probe to 15B (SFI = 1,800) and low affinity to HEK293 (SFI = 300), representing the functionality and specificity of the probe at the molecular level. Sample T1 relaxation times in vitro were 1,600 ms, 1,100 ms, and 450 ms for cells without any probe, HEK293 with probe, and 15B with probe, respectively. The tumor region of interest (ROI) showed strong contrast enhancement following a tail vein injection of the probe. A time course measurement of contrast showed that the image contrast (IC) in the tumor ROI region increased substantially in the first 5 mins after probe injection and kept stable thru the first 40 mins relative to IC in the non-tumor ROI. In a control experiment, IC increased on the mouse injected with the same dose of Gd-DTPA, but subsided after 5 mins. We have developed an EGFR targeting and imaging probe by combining the therapeutic antibody and diagnostic contrast agent Gd for MR imaging. The probe is able to selectively target the EGFR receptor and allow drug uptake to be imaged." @default.
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• W2333178407 date "2012-11-01" @default.
• W2333178407 modified "2023-10-18" @default.
• W2333178407 title "Multifunctional Molecular Probes for Targeting and Imaging of Epidermal Growth Factor Receptor" @default.
• W2333178407 doi "https://doi.org/10.1016/j.ijrobp.2012.07.1840" @default.
• W2333178407 hasPublicationYear "2012" @default.
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