NIR fluorescent dyes (650C800 nm) are preferred based on their depth of penetration [44]. cumulative results indicate that fluorescent-conjugated anti-CEA antibodies have important potential to improve cancer diagnosis and surgery. In an emerging technology, anti-CEA fluorescent antibodies have also been successfully used for photoimmunotherapy treatment for cancer. Keywords: carcinoembryonic antigen, CEA, fluorescence-guided surgery, FGS, infrared dyes, fluorescence, fluorescence labeling 1. Introduction A major barrier to accurate cancer diagnosis and effective treatment is the inability to completely visualize the tumor. This is especially KT 5823 CAPN2 true of metastatic disease. Surgical resection remains a cornerstone of treatment for solid organ tumors. To achieve complete (R0) resection, the surgeon relies upon tactile and visual cues, preoperative imaging and his or her own experience [1,2]. The presence or absence of metastatic disease is critical in determining appropriate surgical treatment. The surgeons ability to accurately determine a tumors margin and identify metastatic lesions is usually paramount [3]. Failure to achieve R0 resection, often due to the invisibility of the tumor margin, is associated with disease recurrence [4,5]. Diagnostic laparoscopy is usually often used to detect metastatic disease, which can be essentially invisible, leading to unnecessary resection of the primary tumor. Cancer diagnosis and treatment can be greatly improved by making the invisible disease visible. Fluorescence labeling of tumors can assist in achieving R0 resection and identifying metastatic lesions. Fluorescence is usually more sensitive than bright-light visualization and palpation in an intraoperative setting [3]. In fluorescence studies, the tumor-to-background-ratio (TBR) is an important concept. Fluorescence studies report the contrast ratio of the tumor signal and KT 5823 signal from normal tissue (background) to quantify results [1]. Initial studies focused on non-specific fluorescent dyes, relying on the enhanced permeability and retention (EPR) effect of tumors to create a contrast between tumor and normal tissue [2]. The most salient example of this is indocyanine green (ICG). ICG has been used for sentinel lymph node detection in breast [6] and gastric cancer [7], as well as liver tumor resection [8]. ICG is also starting to be used for head and neck medical procedures [9]. Oral administration of 5-aminolevulinic acid (5-ALA) is usually another fluorescent probe being KT 5823 used clinically. 5-ALA can help delineate malignant glioblastoma from normal brain tissue [10,11]. However, the lack of specificity of these probes limits their use in other types of cancer. Recent studies use near-infrared (NIR) dyes, which improve tissue penetration due to lack of tissue autofluorescence. The NIR dyes are attached to a monoclonal antibody to a tumor antigen targeting the tumor of interest. One of the most common antibody targets is usually carcinoembryonic antigen (CEA). CEA is usually a membrane-bound glycoprotein expressed in over 80% of colorectal cancers [12]. Although originally associated with colorectal cancer (CRC), it has subsequently been found in lung, breast, pancreatic, gallbladder, bladder, KT 5823 ovarian and gastric cancer [13]. CEA belongs to a family of glycoproteins called carcinoembryonic antigen cell adhesion molecules (CEACAM) and is also known as CEACAM5 and CD66e [14]. Several other CEACAMs have been validated as clinical biomarkers and therapeutic targets in addition to CEA [14]. In the present review, preclinical and clinical studies developing anti-CEA fluorescent antibodies for cancer diagnosis and treatment are reviewed. This review is usually broadly divided into CRC, pancreatic cancer and gastric cancer/other. Within each group, preclinical studies (subcutaneous, orthotopic and intraperitoneal (IP) murine models) and clinical studies using anti-CEA fluorescent antibodies are reviewed. 2. Materials and Methods Two databases (PubMed and Google Scholar) were accessed in August 2021. Inclusion criteria included: (1) use of a specific anti-CEA probe with a fluorescent dye, (2) in vivo imaging, (3) original research study, (4) non-retracted and (5) accessible by the KT 5823 University of California, San Diego (UCSD) library. Exclusion criteria included: (1) nonspecific anti-CEA probes (probes to.