Data from First Clinical Results of Fluorescence Lifetime-enhanced Tumor Imaging Using Receptor-targeted Fluorescent Probes

作者：Rahul Pal, Marisa E. Hom, Nynke S. van den Berg, Thinzar M. Lwin, Yujin Lee, Andrey Prilutskiy, William C. Faquin, Eric H. Yang, Srinivas Vinod Saladi, Mark A. Varvares, Eben L. Rosenthal, Anand T. N. Kumar · 年份：2023 · DOI：10.1158/1078-0432.c.6532280.v1 · 被引用次数：1 · 研究领域：Nanoplatforms for cancer theranostics、Click Chemistry and Applications、Cancer Research and Treatments

<div>AbstractPurpose: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.Experimental Design:We performed wide-field and microscopic FLT imaging of resection specimens from patients injected with panitumumab-IRDye800CW under an FDA directed clinical trial.Results: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 t...