短波红外（900-1,700 nm）荧光成像（SWIRFI）显示出相较于可见光（400-650 nm）和近红外（700-900 nm）荧光成像具有显著优势（自体荧光降低、对比度、组织分辨率和深度敏感性提高）。然而，临床领域在预临床SWIRFI系统和靶向SWIRFI探针的转化方面存在重大滞后。方法: 我们通过临床试验的低酸插入pHLIP肽与吲哚菁绿（ICG）结合（pHLIP ICG），在预临床阶段显示其是癌症靶向SWIRFI的优秀候选物。结果: pHLIP ICG SWIRFI在正位移乳腺癌小鼠模型中，达到了皮摩尔级敏感度（0.4 nM），在注射后96小时内实现了二值和明确的肿瘤筛查和切除。SWIRFI肿瘤筛查和切除具有环境光抗干扰的特点（无需门控或过滤），并在曝光时间从10到0.1 ms下表现出杰出的信噪比（SNR）和对比度噪音比（CNR）值。这些SNR和CNR值也在pHLIP ICG在体内的扩展发射波长（>1,100 nm，300 ms）下得到验证。结论: SWIRFI的敏感性和抗环境光的特性使得可以以视频的速率进行示踪物剂清除追踪，并获得无与伦比的SNR和 CNR值，以实现肿瘤划定（使肿瘤与肌肉比率超过20）。总之，我们提供了抗环境光SWIRFI和pHLIP ICG生态系统民主化转化的直接先例，该系统可以即时提高肿瘤切除手术的效果。 ©2023年核医学与分子成像协会。

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.© 2023 by the Society of Nuclear Medicine and Molecular Imaging.