Glycan-Based Near-infrared Fluorescent (NIRF) Imaging of Gastrointestinal Tumors: a Preclinical Proof-of-Concept In Vivo Study.
Glycan-Based Near-infrared Fluorescent (NIRF) Imaging of Gastrointestinal Tumors: a Preclinical Proof-of-Concept In Vivo Study.
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DOI：
10.1007/s11307-020-01522-8
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发表时间：
2020-12
影响因子：
3.1
通讯作者：
Sier CFM
中科院分区：
文献类型：
--
作者：
Houvast RD;Baart VM;Bhairosingh SS;Cordfunke RA;Chua JX;Vankemmelbeke M;Parsons T;Kuppen PJK;Durrant LG;Vahrmeijer AL;Sier CFM
Aberrantly expressed glycans in cancer are of particular interest for tumor targeting. This proof-of-concept in vivo study aims to validate the use of aberrant Lewis glycans as target for antibody-based, real-time imaging of gastrointestinal cancers. Immunohistochemical (IHC) staining with monoclonal antibody FG88.2, targeting Lewisa/c/x, was performed on gastrointestinal tumors and their healthy counterparts. Then, FG88.2 and its chimeric human/mouse variant CH88.2 were conjugated with near-infrared fluorescent (NIRF) IRDye 800CW for real-time imaging. Specific binding was evaluated in vitro on human gastrointestinal cancer cell lines with cell-based plate assays, flow cytometry, and immune-fluorescence microscopy. Subsequently, mice bearing human colon and pancreatic subcutaneous tumors were imaged in vivo after intravenous administration of 1 nmol (150 μg) CH88.2-800CW with the clinical Artemis NIRF imaging system using the Pearl Trilogy small animal imager as reference. One week post-injection of the tracer, tumors and organs were resected and tracer uptake was analyzed ex vivo. IHC analysis showed strong FG88.2 staining on colonic, gastric, and pancreatic tumors, while staining on their normal tissue counterparts was limited. Next, human cancer cell lines HT-29 (colon) and BxPC-3 and PANC-1 (both pancreatic) were identified as respectively high, moderate, and low Lewisa/c/x-expressing. Using the clinical NIRF camera system for tumor-bearing mice, a mean tumor-to-background ratio (TBR) of 2.2 ± 0.3 (Pearl: 3.1 ± 0.8) was observed in the HT-29 tumors and a TBR of 1.8 ± 0.3 (Pearl: 1.9 ± 0.5) was achieved in the moderate expression BxPC-3 model. In both models, tumors could be adequately localized and delineated by NIRF for up to 1 week. Ex vivo analysis confirmed full tumor penetration of the tracer and low fluorescence signals in other organs. Using a novel chimeric Lewisa/c/x-targeting tracer in combination with a clinical NIRF imager, we demonstrate the potential of targeting Lewis glycans for fluorescence-guided surgery of gastrointestinal tumors. The online version of this article (10.1007/s11307-020-01522-8) contains supplementary material, which is available to authorized users.
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影响因子：
4.8
作者：
GERSTEN, KM;NATSUKA, S;LOWE, JB
通讯作者：
LOWE, JB
DOI：
10.1073/pnas.82.11.3552
发表时间：
1985-01-01
影响因子：
11.1
作者：
BLASZCZYK, M;PAK, KY;STEPLEWSKI, Z
通讯作者：
STEPLEWSKI, Z
影响因子：
--
作者：
Handgraaf HJM;Boonstra MC;Prevoo HAJM;Kuil J;Bordo MW;Boogerd LSF;Sibinga Mulder BG;Sier CFM;Vinkenburg-van Slooten ML;Valentijn ARPM;Burggraaf J;van de Velde CJH;Frangioni JV;Vahrmeijer AL
通讯作者：
Vahrmeijer AL
影响因子：
2.3
作者：
Boogerd, Leonora S. F.;Boonstra, Martin C.;Vahrmeijer, Alexander L.
通讯作者：
Vahrmeijer, Alexander L.
影响因子：
9.7
作者：
Pinho, Sandra;Marcos, Nuno T.;Reis, Celso A.
通讯作者：
Reis, Celso A.