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Molecular Targeted NIR-II Probe for Image-Guided Brain Tumor Surgery

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  1. Preclinical Study on GRPR-Targeted (68)Ga-Probes for PET Imaging of Prostate Cancer

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  2. Synthesis and Evaluation of Astatinated N-[2-(Maleimido)ethyl]-3-(trimethylstannyl)benzamide Immunoconjugates

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  3. NMR characterization of the DNA binding properties of a novel Hoechst 33258 analogue peptide building block

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  4. Concerted intercalation and minor groove recognition of DNA by a homodimeric thiazole orange dye

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  1. Near-infrared fluorescence imaging improves the nodal yield in neck dissection in oral cavity cancer - A randomized study

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  2. Evolution and Medical Significance of LU Domain-Containing Proteins

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  3. Cardiac Autonomic Function is Associated With Myocardial Flow Reserve in Type 1 Diabetes

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  4. Did evolution create a flexible ligand-binding cavity in the urokinase receptor through deletion of a plesiotypic disulfide bond?

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Optical imaging strategies for improving delineation of glioblastoma (GBM) is highly desired for guiding surgeons to distinguish cancerous tissue from healthy and precious brain tissue. Fluorescence imaging (FLI) in the second near-infrared window (NIR-II) outperforms traditional NIR-I imaging with better tissue penetration, higher spatial and temporal resolution, and less auto fluorescence and scattering. Because of high expression in GBM and many other tumors, urokinase Plasminogen Activator Receptor (uPAR) is an attractive and well proven target for FLI. Herein we aim to combine the benefit of a NIR-II fluorophore with a high affinity uPAR targeting small peptide. A targeted NIR-II fluorescent probe was developed by conjugating an in-house synthesized NIR-II fluorophore, CH1055, and a uPAR targeting peptide, AE105. To characterize the in vivo distribution and targeting properties, a dynamic imaging was performed in orthotopic GBM bearing nude mice ( n = 8). Additionally, fluorescence guided surgery of orthotopic GBM was performed in living animals. CH1055-4Glu-AE105 was easily synthesized with >75% yield and >98% HPLC evaluated purity. The retention time of the probe on analytical HPLC was 15.9 min and the product was verified by mass spectrometry. Dynamic imaging demonstrated that the uPAR targeting probe visualized orthotopic GBM through the intact skull with a tumor-to-background ratio (TBR) of 2.7 peaking at 96 h. Further, the orthotopic GBM was successfully resected in small animals guided by the NIR-II FLI. By using a small uPAR targeting NIR-II probe, FLI allows us to specifically image and detect GBM. A real-time imaging setup further renders FLI guided tumor resection, and the probe developed in this work is a promising candidate for clinical translation.

Original languageEnglish
JournalBioconjugate Chemistry
Volume29
Issue number11
Pages (from-to)3833-3840
Number of pages8
ISSN1043-1802
DOIs
Publication statusPublished - 21 Nov 2018

ID: 56600034