Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Department of Otolaryngology-Head and Neck Surgery, Vanderbilt University Medical Center, Nashville, Tennessee.
Clin Cancer Res. 2022 Jun 1;28(11):2373-2384. doi: 10.1158/1078-0432.CCR-21-3429.
Fluorescence molecular imaging, using cancer-targeted near infrared (NIR) fluorescent probes, offers the promise of accurate tumor delineation during surgeries and the detection of cancer specific molecular expression in vivo. However, nonspecific probe accumulation in normal tissue results in poor tumor fluorescence contrast, precluding widespread clinical adoption of novel imaging agents. Here we present the first clinical evidence that fluorescence lifetime (FLT) imaging can provide tumor specificity at the cellular level in patients systemically injected with panitumumab-IRDye800CW, an EGFR-targeted NIR fluorescent probe.
We performed wide-field and microscopic FLT imaging of resection specimens from patients injected with panitumumab-IRDye800CW under an FDA directed clinical trial.
We show that the FLT within EGFR-overexpressing cancer cells is significantly longer than the FLT of normal tissue, providing high sensitivity (>98%) and specificity (>98%) for tumor versus normal tissue classification, despite the presence of significant nonspecific probe accumulation. We further show microscopic evidence that the mean tissue FLT is spatially correlated (r > 0.85) with tumor-specific EGFR expression in tissue and is consistent across multiple patients. These tumor cell-specific FLT changes can be detected through thick biological tissue, allowing highly specific tumor detection and noninvasive monitoring of tumor EFGR expression in vivo.
Our data indicate that FLT imaging is a promising approach for enhancing tumor contrast using an antibody-targeted NIR probe with a proven safety profile in humans, suggesting a strong potential for clinical applications in image guided surgery, cancer diagnostics, and staging.
荧光分子成像技术，使用针对近红外（NIR）荧光探针的癌症靶向，有望在手术过程中准确描绘肿瘤，并在体内检测到癌症特异性分子表达。然而，由于正常组织中探针的非特异性积累，导致肿瘤荧光对比度较差，从而阻止了新型成像剂的广泛临床应用。在这里，我们首次提供临床证据表明，荧光寿命（FLT）成像可以在全身注射 EGFR 靶向 NIR 荧光探针 panitumumab-IRDye800CW 的患者中，在细胞水平上提供肿瘤特异性。
我们在 FDA 指导的临床试验下，对注射 panitumumab-IRDye800CW 的患者的切除标本进行了广角和显微镜 FLT 成像。
我们表明，过度表达 EGFR 的癌细胞中的 FLT 明显长于正常组织中的 FLT，尽管存在明显的非特异性探针积累，但对肿瘤与正常组织分类具有高灵敏度（>98%）和特异性（>98%）。我们进一步表明，微观证据表明，组织中的平均组织 FLT 与组织中肿瘤特异性 EGFR 表达具有空间相关性（r > 0.85），并且在多个患者中是一致的。这些肿瘤细胞特异性 FLT 变化可以通过厚的生物组织检测到，允许对体内肿瘤 EFGR 表达进行高度特异性肿瘤检测和非侵入性监测。
我们的数据表明，FLT 成像技术是一种很有前途的方法，可使用已在人体中具有良好安全性的抗体靶向 NIR 探针增强肿瘤对比度，这表明其在图像引导手术、癌症诊断和分期方面具有很强的临床应用潜力。
