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. 2021 Dec 2;11(12):1819. doi: 10.3390/biom11121819

Table 1.

List of anti-CEA fluorescent antibody studies.

Title Author Year Model Antibody Dye Dose Timing Tumor
Antibody-fluorescein conjugates for photoimmunodiagnosis of human colon carcinoma in nude mice [15] Pèlegrin, A. 1991 Mice MoAB 35 (Murine) Fluorescein 20 μg 6–96 h T380 (human CRC) subcutaneous (SQ)
Immunophotodiagnosis of colon carcinomas in patients injected with fluoresceinated chimeric antibodies against carcinoembryonic antigen [39] Folli, S. 1992 Human CGP44290 (Murine) Fluorescein isothyocyanate 4.5 mg
9 mg
24 h known primary CRC
Direct in vivo measurement of targeted binding in a human tumor xenograft [16] Berk, D.A. 1997 Mice ZCE025
(Murine)
Fluorescein 20–6000 μg 10 m–24 h LS174T SQ
Intraoperative immunophotodetection for radical resection of cancers [26] Gutowski, M. 2001 Mice 35A7
(Murine)
ICG 10, 40, 100 μg 48 h LS174T IP cell injection
Fluorescence endoscopy using a fluorescein-labeled monoclonal antibody against carcinoembryonic antigen in patients with colorectal carcinoma and adenoma [40] Keller, R. 2002 Human Monoclonal (Murine) FLOUS 2–6 mL 10 min 27 patients with large colonic lesions
In vivo near-infrared fluorescence imaging of carcinoembryonic antigen-expressing tumor cells in mice [17] Lisy, M. 2008 Mice Arcitumomab (Chimeric) DY-676 40 μg 2–24 h LS174T SQ
Fluorophore-conjugated anti-CEA antibody for the intraoperative imaging of pancreatic and colorectal cancer [18] Kaushal, S. 2008 Mice Monoclonal (Murine) AlexaFluor 488 75 μg 24 h BxPC3 SQ
Colo4104 (CRC) SQ and cecal orthotopic
An LED light source and novel fluorophore combinations improve fluorescence laparoscopic detection of metastatic pancreatic cancer in orthotopic mouse models [45] Metildi, C. 2012 Mice Monoclonal (Murine) Alexa 448
Alexa 555
75 μg 24 h BxPC3 pancreatic orthotopic
Tumor-specific fluorescence antibody imaging enables accurate staging laparoscopy in an orthotopic model of pancreatic cancer [46] Tran Cao, H.S. 2012 Mice Monoclonal (Murine) Alexa Fluor 488 75 μg 24 h BxPC3 pancreatic orthotopic
BxPC3 IP cell injection
New whole-body multimodality imaging of gastric cancer peritoneal metastasis combining fluorescence imaging with ICG-labeled antibody and MRI in mice [57] Ito, A. 2013 Mice HB 8747 (Murine) XenoLight CF750 0.05 mg 10 m–7 d MKN-28 (gastric cancer cell line), GCIY (gastric cancer cell line), GLM-1, GLM -2 (patient derived gastric cancer liver metastasis)
IP models
Comparison of a chimeric anti-carcinoembryonic antigen antibody conjugated with visible or near-infrared fluorescent dyes for imaging pancreatic cancer in orthotopic nude mouse models [44] Maawy, A. 2013 Mice Monoclonal (Chimeric) 488 nm, 550 nm, 650 nm, 750 nm 50–75 μg (1.25 μmol of dye) 24 h BxPC3 pancreatic orthotopic
SPECT- and fluorescence image-guided surgery using a dual-labeled carcinoembryonic antigen-targeting antibody [27] Rijpkema, M. 2014 Mice MN-14 (Murine) IRDye 800CW 1–100 μg 1–8 d LS174T SQ cell injection
LS174T IP cell injection
Fluorescently labeled chimeric anti-CEA antibody improves detection and resection of human colon cancer in a patient-derived orthotopic xenograft (PDOX) nude mouse model [21] Metildi, C. 2014 Mice Monoclonal (Chimeric) Alexa Fluor 488 75 μg 24 h Patient derived (PD) CRC orthotopic
Successful fluorescence-guided surgery on human colon cancer patient-derived orthotopic xenograft mouse models using a fluorophore-conjugated anti-CEA antibody and a portable imaging system [22] Hiroshima, Y. 2014 Mice Monoclonal (Murine) Alexa Fluor 488 Unspecified 24 h PD CRC
Specific tumor labeling enhanced by polyethylene glycol linkage of near-infrared dyes conjugated to a chimeric anti-carcinoembryonic antigen antibody in a nude mouse model of human pancreatic cancer [43] Maawy, A. 2014 Mice Monoclonal (Chimeric) DyLight 650/750
DyLight 650/750 PEG
2.5 nmol 5 m–24 h BxPC3 SQ
Polyethylene glycol (PEG) linked to near-infrared (NIR) dyes conjugated to chimeric Anti-Carcinoembryonic Antigen (CEA) antibody enhances imaging of liver metastases in a nude-mouse model of human colon cancer [29] Maawy, A. 2014 Mice Monoclonal (Chimeric) DyLight 650/750
DyLight 650/750 PEG
2.5 nmol (94 μg) 24 h HT29 spleen injection
Advantages of fluorescence-guided laparoscopic surgery of pancreatic cancer labeled with fluorescent anti-carcinoembryonic antigen antibodies in an orthotopic mouse model [47] Metildi, C. 2014 Mice Monoclonal (Chimeric) Alexa Fluor 488 75 μg 24 h BxPC3-RFP pancreatic orthotopic
Fluorescence-guided surgery with a fluorophore-conjugated antibody to carcinoembryonic antigen (CEA), that highlights the tumor, improves surgical resection and increases survival in orthotopic mouse models of human pancreatic cancer [48] Metildi, C. 2014 Mice Monoclonal
(Chimeric)
Alexa Fluor 488 75 μg 24 h BxPC3-RFP pancreatic ortho
Potent and specific antitumor effect of CEA-targeted photoimmunotherapy [33] Shirasu, N. 2014 Mice C2-45
(Human)
IRDye 700DX NHS Ester 100, 200 μg 24 h MKN-45-luc (gastric cancer) SQ cell injection
In vivo subcellular imaging of tumors in mouse models using a fluorophore-conjugated anti-carcinoembryonic antigen antibody in two-photon excitation microscopy [56] Koga, S. 2014 Mice CB30
(Murine)
Alexa 594 10, 50 μg 24 h HT1080 (human fibrosarcoma) SQ cell injection
MKN45 (human gastric) SQ cell injection
Metastatic recurrence in a pancreatic cancer patient-derived orthotopic xenograft (PDOX) nude mouse model is inhibited by neoadjuvant chemotherapy in combination with fluorescence-guided surgery with an anti-CA 19-9-conjugated fluorophore. [51] Hiroshima, Y. 2014 Mice Monoclonal
(Chimeric)
DyLight 650 50 μg 24 h PD pancreatic cancer patient-derived orthotopic xenograft (PDOX)
Fluorescence-guided surgery, but not bright-light surgery, prevents local recurrence in a pancreatic cancer patient-derived orthotopic xenograft (PDOX) model resistant to neoadjuvant chemotherapy (NAC) [52] Hiroshima, Y. 2015 Mice Monoclonal
(Chimeric)
DyLight 650 50 μg 24 h PD pancreatic cancer PDOX
Near-infrared photoimmunotherapy with anti-CEA-IR700 results in extensive tumor lysis and a significant decrease in tumor burden in orthotopic mouse models of pancreatic cancer [54] Maawy, A. 2015 Mice Monoclonal
(Chimeric)
IRDye 700DX NHS Ester 100 μg 24 h BxPC3 pancreatic orthotopic
Preclinical evaluation of a novel CEA-targeting near-infrared fluorescent tracer delineating colorectal and pancreatic tumors [23] Boonstra, M. 2015 Mice ssSM3E
(Humanized)
IRDye 800CW 28 μg 8–120 h HT29 cecal orthotopic
BxPC3 cell injection pancreatic ortho
Effective fluorescence-guided surgery of liver metastasis using a fluorescent anti-CEA antibody [25] Hiroshima, Y. 2016 Mice Monoclonal
(Chimeric)
DyLight 650 50 μg 24 h–72 h HT29 liver orthotopic and liver metastasis spleen injection
Development and evaluation of a fluorescent antibody-drug conjugate for molecular imaging and targeted therapy of pancreatic cancer [42] Knutson, S. 2016 Mice Monoclonal
(Murine)
DyLight-680-4xPEG 100 μg 24 h BxPC3 SQ
Near-infrared-conjugated humanized anti-carcinoembryonic antigen antibody targets colon cancer in an orthotopic nude-mouse model [24] DeLong, J. 2017 Mice M5A
(Humanized)
NHS-IRDye 800CW 75 μg 24–48 h HT29 cecal orthotopic
Detection of micrometastases using SPECT/fluorescence dual-modality imaging in a CEA-expressing tumor model [28] Hekman, M. 2017 Mice Labetuzumab
(Humanized)
IRDye 800CW 10 μg 3 d GW-39 (human CRC) cell injection lung metastasis
SGM-101: An innovative near-infrared dye-antibody conjugate that targets CEA for fluorescence-guided surgery [30] Gutowski, M. 2017 Mice SGM-ch511
(Chimeric)
BM104 30 μg 24 h–96 h LS174T IP model
HT29 cecal orthotopic
LS174T liver metastasis via spleen
BxPC3 pancreatic orthotopic
A Dual Reporter Iodinated Labeling Reagent for Cancer Positron Emission Tomography Imaging and Fluorescence-Guided Surgery [20] Lu, Z. 2018 Mice A5B7
(Murine)
I-Green 44 μg 72 h SW1222 CRC SQ
Safety and effectiveness of SGM-101, a fluorescent antibody targeting carcinoembryonic antigen, for intraoperative detection of colorectal cancer: a dose-escalation pilot study [36] Boogerd, L.S.F. 2018 Human SGM-ch511
(Chimeric)
BM104 5–10 mg 48 h–96 h CRC
Image-guided surgery in patients with pancreatic cancer: First results of a clinical trial using SGM-101, a novel carcinoembryonic antigen-targeting, near-infrared fluorescent agent [55] Hoogstins, C. 2018 Human SGM-ch511
(Chimeric)
BM104 5, 7.5, 10 mg 48 h, 96 h PDAC
Fluorescent humanized anti-CEA antibody specifically labels metastatic pancreatic cancer in a patient-derived orthotopic xenograft (PDOX) mouse model [53] Lwin, T.M. 2018 Mice M5A
(Humanized)
IRDye 800CW 75 μg 48 h PD pancreatic PDOX
Tumor-specific labeling of pancreatic cancer using a humanized anti-CEA antibody conjugated to a near-infrared fluorophore [49] Lwin, T.M. 2018 Mice M5A
(Humanized)
IRDye 800CW 75 μg 6–96 h BxPC3 pancreatic orthotopic
Improved antibody-guided surgery with a near-infrared dye on a pegylated linker for CEA-positive tumors [50] Yazaki, P.J. 2019 Mice M5A
(Humanized)
NHS-IRDye 800CW PEGylated 75 μg 24–96 h BxPC3 pancreatic orthotopic
Carcinoembryonic antigen-targeted photodynamic therapy in colorectal cancer models [34] Elekonawo, F. 2019 Mice Labetuzumab
(Humanized)
IRDye 700DX NHS Ester 30 μg LOVO SQ cell injection
Near-infrared photoimmunotherapy is effective treatment for colorectal cancer in orthotopic nude-mouse models [35] Hollandsworth, H.M. 2020 athymic nude mice M5A
(Humanized)
IRDye 700DX NHS Ester 50 μg 24 h LS174T cecal orthotopic
Carcinoembryonic antigen-specific, fluorescent image-guided cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for metastatic colorectal cancer [38] Schaap, D.P. 2020 Human SGM-ch511
(Chimeric)
BM104 10–15 mg 4–6 d peritoneal metastatic CRC
Multimodal image-guided surgery of colorectal peritoneal carcinomatosis: a phase 1 clinical trial [41] Elekonawo, F. 2020 Human Labetuzumab
(Humanized)
IRDye 800CW 2 or 5 mg 5–6 days Colorectal peritoneal metastasis
Near-infrared fluorescent imaging of pancreatic cancer in mice using a novel antibody to CEACAM 5 [19] Zhou, X. 2021 Mice C1P83 IRDye 800CW 25 μg (SQ model)
25, 100 μg (ortho)
24 h–6 d C15A3 CRC SQ
BxPC3 pancreatic orthotopic
Spectrally distinct double labeling of colon-cancer liver metastases and adjacent liver segment with a near-infrared-labeled anti-Carcinoembryonic antigen (CEA_ antibody and indocyanine green in an orthotopic mouse model. [31] Nishino, H. 2021 Mice SGM-ch511
(Chimeric)
BM104 Unspecified 48 h–96 h LS174T liver orthotopic
Dose-finding study of a CEA-targeting agent, SGM-101, for intraoperative fluorescence imaging of colorectal cancer [37] de Valk, K. 2021 Human SGM-ch511
(Chimeric)
BM104 5–15 mg 24 h–6 d CRC