Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, New York;
Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, New York.
J Nucl Med. 2023 Oct;64(10):1647-1653. doi: 10.2967/jnumed.123.265686. Epub 2023 Aug 24.
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. 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. 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). 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.
短波近红外（900-1700nm）荧光成像是（SWIRFI）在可见（400-650nm）和近红外（700-900nm）荧光成像方面显示出了重大优势（减少自发荧光、提高对比度、组织分辨率和深度灵敏度）。然而，临床转化前临床 SWIRFI 系统和靶向 SWIRFI 探针的速度明显滞后。我们临床前研究表明，目前正在临床试验中的 pH 低插入肽缀合吲哚菁绿（pHLIP ICG）是癌症靶向 SWIRFI 的绝佳候选物。pHLIP ICG SWIRFI 实现了皮摩尔灵敏度（0.4nM），可进行二进制和明确的肿瘤筛选和切除，在荷乳腺癌小鼠模型中注射后 96 小时仍可进行。SWIRFI 肿瘤筛选和切除具有环境光抗干扰性（无需门控或滤波即可实现），在 10 至 0.1ms 的曝光下具有出色的信噪比（SNR）和对比噪声比（CNR）值。在 pHLIP ICG 的扩展发射（体内>1100nm，300ms）中也发现了这些 SNR 和 CNR 值。SWIRFI 的灵敏度和环境光抗干扰性使我们能够继续追踪示踪剂清除情况，并以无与伦比的 SNR 和 CNR 值在视频率下进行肿瘤描绘，实现肿瘤与肌肉的比值超过 20。总的来说，我们为具有环境光抗干扰性的 SWIRFI 和 pHLIP ICG 生态系统的民主转化提供了直接先例，这可以立即提高肿瘤切除率。
