Abstract
Pancreatic cancer is a highly lethal disease in part due to incomplete tumor resection. Targeting by tumor-specific antibodies conjugated with a fluorescent label can result in selective labeling of cancer in vivo for surgical navigation. In the present study, we describe a patient-derived orthotopic xenograft model of pancreatic cancer that recapitulated the disease on a gross and microscopic level, along with physiologic clinical manifestations. We additionally show that the use of an anti-CEA antibody conjugated to the near-infrared (NIR) fluorescent dye, IRDye800CW, can selectively highlight the pancreatic cancer and its metastases in this model with a tumor-to-background ratio of 3.5 (SEM 0.9). The present results demonstrate the clinical potential of this labeling technique for fluorescence-guided surgery of pancreatic cancer.
Highlights
Fluorescence guided surgery (FGS) using nearinfrared fluorophores (NIR) conjugated to tumor-specific antibodies can assist in visualization of the pancreatic cancer and any intra-abdominal metastases that would preclude the patient from an invasive and ineffective surgical procedure [6]
We show that a fluorescent humanized anti-Carcinoembryonic antigen (CEA) antibody labels the primary neoplasm as well as submillimeter satellite lesions that would otherwise be missed by bright-light imaging and the naked eye
We described a patient derived orthotopic xenograft (PDOX) model of metastatic pancreatic cancer established from a patient surgical specimen and used this PDOX model to demonstrate the ability of a humanized anti-CEA antibody conjugated to a NIR fluorophore to target the primary tumor and even micro-metastases
Summary
Most pancreatic resections are incomplete as these visual and tactile cues may miss the tumor margin as well as small metastases, especially sub-centimeter lesions not detectable by pre-operative imaging modalities and this has an impact on patient outcomes [2–5]. Fluorescence guided surgery (FGS) using nearinfrared fluorophores (NIR) conjugated to tumor-specific antibodies can assist in visualization of the pancreatic cancer and any intra-abdominal metastases that would preclude the patient from an invasive and ineffective surgical procedure [6]. Current FDA approved NIR fluorophores include indocyanine green and methylene blue. Conjugation of NIR-fluorophores to antibodies allows selective labeling of tumors and metastases [8]
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