First clinical results of fluorescence lifetime-enhanced tumor imaging using receptor targeted fluorescent probes.

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, non-specific 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 epidermal growth factor receptor (EGFR) targeted NIR fluorescent probe.We performed wide-field and microscopic fluorescence lifetime 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 vs. normal tissue classification, despite the presence of significant non-specific 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 non-invasive 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.