Intraoperative Pancreatic Cancer Detection using Tumor-Specific Multimodality Molecular Imaging

Abstract

Background Operative management of pancreatic ductal adenocarcinoma (PDAC) is complicated by several key decisions during the procedure. Identification of metastatic disease at the outset and, when none is found, complete (R0) resection of primary tumor are key to optimizing clinical outcomes. The use of tumor-targeted molecular imaging, based on photoacoustic and fluorescence optical imaging, can provide crucial information to the surgeon. The first-in-human use of multimodality molecular imaging for intraoperative detection of pancreatic cancer is reported using cetuximab-IRDye800, a near-infrared fluorescent agent that binds to epidermal growth factor receptor. Methods A dose-escalation study was performed to assess safety and feasibility of targeting and identifying PDAC in a tumor-specific manner using cetuximab-IRDye800 in patients undergoing surgical resection for pancreatic cancer. Patients received a loading dose of 100 mg of unlabeled cetuximab before infusion of cetuximab-IRDye800 (50 mg or 100 mg). Multi-instrument fluorescence imaging was performed throughout the surgery in addition to fluorescence and photoacoustic imaging ex vivo. Results Seven patients with resectable pancreatic masses suspected to be PDAC were enrolled in this study. Fluorescence imaging successfully identified tumor with a significantly higher mean fluorescence intensity in the tumor (0.09 ± 0.06) versus surrounding normal pancreatic tissue (0.02 ± 0.01), and pancreatitis (0.04 ± 0.01; p < 0.001), with a sensitivity of 96.1% and specificity of 67.0%. The mean photoacoustic signal in the tumor site was 3.7-fold higher than surrounding tissue. Conclusions The safety and feasibilty of intraoperative, tumor-specific detection of PDAC using cetuximab-IRDye800 with multimodal molecular imaging of the primary tumor and metastases was demonstrated.

First-in-human intraoperative near-infrared fluorescence imaging of glioblastoma using cetuximab-IRDye800

“…As this is the first in-human study using this technology, it was important to establish a baseline of non-specific fluorescence uptake in non-tumor tissue. This methodology has previously been demonstrated in prior publications in a variety of tumor types [16, 17]. A histologically proven tumor specimen that was fluorescent was considered a true-positive; a histologically normal specimen that was fluorescent was a false-positive; a histologically normal specimen that was non-fluorescent was a true-negative; and a histologically positive tumor that was non-fluorescent was a false-negative.…”

Optical-Resolution Photoacoustic Microscopy Using Transparent Ultrasound Transducer

“…In the future, the proposed TUT could be integrated in conventional optical-microscopy techniques to allow multimodal microscopy that is capable of both ultrasound stimulation and sensing. Eventually, the TUT technology could be further scaled to develop miniaturized photoacoustic endomicroscopy and microendoscopy devices for space-constrained point-of-care clinical applications, e.g., prostate and pancreas needle biopsies [35][36][37].…”

Advanced Nanotechnology Leading the Way to Multimodal Imaging‐Guided Precision Surgical Therapy

“…[115][116][117][118][119][120] Moreover, OTL38, an NIRF agent binding with folate receptor-α has entered Phase III clinical trial stage for patients with ovarian cancer [121] and Phase II clinical trial stage for patients with pulmonary adenocarcinomas. Rosenthal and co-workers devoted a considerable amount of efforts in researching tumor-specific fluorescent probes by conjugating antibodies (e.g., panitumumab, cetuximab, etc.)…”