吲哚青绿
荧光
荧光寿命成像显微镜
化学
体内
材料科学
医学
病理
光学
生物
物理
生物技术
作者
Benedict Mc Larney,Mijin Kim,Sheryl Roberts,Magdalena Skubal,Hsiao-Ting Hsu,Anuja Ogirala,Edwin C. Pratt,Nagavarakishore Pillarsetty,Daniel A. Heller,Jason S. Lewis,Jan Grimm
标识
DOI:10.2967/jnumed.123.265686
摘要
Shortwave infrared (900–1,700 nm) fluorescence imaging (SWIRFI) has shown significant advantages over visible (400–650 nm) and near-infrared (700–900 nm) fluorescence imaging (reduced autofluorescence, improved contrast, tissue resolution, and depth sensitivity). However, there is a major lag in the clinical translation of preclinical SWIRFI systems and targeted SWIRFI probes. Methods: We preclinically show that the pH low-insertion peptide conjugated to indocyanine green (pHLIP ICG), currently in clinical trials, is an excellent candidate for cancer-targeted SWIRFI. Results: pHLIP ICG SWIRFI achieved picomolar sensitivity (0.4 nM) with binary and unambiguous tumor screening and resection up to 96 h after injection in an orthotopic breast cancer mouse model. SWIRFI tumor screening and resection had ambient light resistance (possible without gating or filtering) with outstanding signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) values at exposures from 10 to 0.1 ms. These SNR and CNR values were also found for the extended emission of pHLIP ICG in vivo (>1,100 nm, 300 ms). Conclusion: SWIRFI sensitivity and ambient light resistance enabled continued tracer clearance tracking with unparalleled SNR and CNR values at video rates for tumor delineation (achieving a tumor-to-muscle ratio above 20). In total, we provide a direct precedent for the democratic translation of an ambient light resistant SWIRFI and pHLIP ICG ecosystem, which can instantly improve tumor resection.
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