scholarly journals CF750-A33scFv-Fc-Based Optical Imaging of Subcutaneous and Orthotopic Xenografts of GPA33-Positive Colorectal Cancer in Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Danfeng Wei ◽  
Qing Fan ◽  
Huawei Cai ◽  
Hao Yang ◽  
Lin Wan ◽  
...  

Antibody-based imaging agents are attractive as adjuvant diagnostic tools for solid tumors. GPA33 is highly expressed in most human colorectal cancers and has been verified as a diagnostic and therapeutic target. Here, we built an A33scFv-Fc antibody against GPA33 by fusing A33scFv to the Fc fragment of human IgG1 antibodies. The A33scFv-Fc specifically binds GPA33-positive colorectal cancer cells and tumor tissues. After the intravenous injection of mice bearing subcutaneous GPA33-positive LS174T tumor grafts with near-infrared fluorescence probe CF750-labeled A33scFv-Fc (CF750-A33scFv-Fc), high contrast images of the tumor grafts could be kinetically documented within 24 h using an optical imaging system. However, GPA33-negative SMMC7721 tumor grafts could not be visualized by injecting the same amount of CF750-A33scFv-Fc. Moreover, in subcutaneous LS174T tumor-bearing mice, tissue scanning revealed that the CF750-A33scFv-Fc accumulated in the tumor grafts, other than the kidney and liver. In mice with orthotopic tumor transplantations, excrescent LS174T tumor tissues in the colon were successfully removed under guidance by CF750-A33scFv-Fc-based optical imaging. These results indicate that CF750-A33scFv-Fc can target GPA33, suggesting the potential of CF750-A33scFv-Fc as an imaging agent for the diagnosis of colorectal cancer.

2019 ◽  
Vol 9 (17) ◽  
pp. 3510 ◽  
Author(s):  
Mohammad Wajih Alam ◽  
Khan A. Wahid ◽  
Md. Fahmid Islam ◽  
Wendy Bernhard ◽  
Clarence R. Geyer ◽  
...  

Fluorescence imaging is a well-known method for monitoring fluorescence emitted from the subject of interest and provides important insights about cell dynamics and molecules in mammalian cells. Currently, many solutions exist for measuring fluorescence, but the application methods are complex and the costs are high. This paper describes the design and development of a low-cost, smart and portable fluorimeter for the detection of colorectal cancer cell expressing IRFP702. A flashlight is used as a light source, which emits light in the visible range and acts as an excitation source, while a photodiode is used as a detector. It also uses a longpass filter to only allow the wavelength of interest to pass from the cultured cell. It eliminates the need of both the dichroic mirror and excitation filter, which makes the developed device low cost, compact and portable as well as lightweight. The custom-built sample chamber is black in color to minimize interference and is printed with a 3D printer to accommodate the detector circuitry. An established colorectal cancer cell line (human colorectal carcinoma (HCT116)) was cultured in the laboratory environment. A near-infrared fluorescent protein IRFP702 was expressed in the colorectal cancer cells that were used to test the proof-of-concept. The fluorescent cancer cells were first tested with a commercial imaging system (Odyssey® CLx) and then with the developed prototype to validate the result in a preclinical setting. The developed fluorimeter is versatile as it can also be used to detect multiple types of cancer cells by simply replacing the filters based on the fluorophore.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e11591-e11591
Author(s):  
S. Troyan ◽  
S. Gibbs-Strauss ◽  
S. Gioux ◽  
R. Oketokoun ◽  
F. Azar ◽  
...  

e11591 Background: Breast cancer surgery is presently performed without real-time image-guidance. We have developed a novel optical imaging system for image-guided surgery that uses invisible near-infrared (NIR) fluorescent light to highlight structures on the surgical field with high sensitivity, specificity, and contrast. We have also performed the first human clinical trial of the imaging system in women undergoing SLN mapping for breast cancer. Methods: We used a portable imaging system with an articulating arm that has 6 degrees of freedom, high power LED light source, custom optics, custom software, and sterile drape. The imaging system provided simultaneous and real-time imaging of color video and NIR fluorescence at up to 15 frames per second. N = 6 women with biopsy- confirmed breast cancer undergoing SLN mapping gave informed consent. All subjects received conventional mapping with Tc-99m sulfur colloid using a handheld gamma probe as well as NIR fluorescence-guided SLN mapping using a mixture of indocyanine green (ICG) diluted to a final concentration of 10 μM in human serum albumin (ICG:HSA). Results: The imaging system was easy to position in the operating room, with the articulating arm providing 50” horizontal reach and 70” vertical reach. Working distance to the patient was 18”. NIR fluorescence excitation was 20 mW/cm2 at 760 nm. NIR-depleted white light was 40,000 lux. A total of 1.6 ml of ICG:HSA was injected intra-tumorally and peri-tumorally and the site massaged for 5 min. 8 of 9 SLNs identified by Tc- 99m sulfur colloid were also identified by NIR fluorescence. However, NIR fluorescence identified an SLN, confirmed to have cancer in it, that was not identified by Tc-99m sulfur colloid. These differences were consistent with asynchrony in the injection techniques. Unlike the gamma-ray probe, NIR fluorescence provided high-resolution, large area optical imaging of the surgical field, and helped guide surgical resection. Conclusions: In this 6-patient pilot study, a novel NIR fluorescence optical imaging system was used for the first time, and provided real-time image-guided surgery for SLN mapping of breast cancer. No significant financial relationships to disclose.


2009 ◽  
Vol 02 (02) ◽  
pp. 179-187
Author(s):  
XIUPING LIU ◽  
ZHENGMING XIONG ◽  
SHEEN-WOO LEE ◽  
JELENA LEVI ◽  
SHAHRIAR YAGHOUBI ◽  
...  

The purpose of this study is to investigate whether a near-infrared fluorescence (NIRF) probe, Cy5.5-D-glucosamine (Cy5.5-2DG), can image arthritis in collagen-induced arthritic (CIA) mice. The presence of arthritis was verified by both visual examination and micro-computed tomography (MicroCT) imaging. CIA mice were imaged by a micro-positron emission tomography (MicroPET) scanner one hour after intravenous injection of 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG). After radioactivity of [18F]FDG decayed away, Cy5.5-2DG was injected into a lateral tail vein of the mice. Arthritic tissue targeting and retention of Cy5.5-2DG in CIA mice were evaluated and quantified by an optical imaging system. Inflammatory tissue in CIA mice was clearly visualized by [18F]FDG-MicroPET scan. NIRF imaging of Cy5.5-2DG in the same mice revealed that the pattern of localization of Cy5.5-2DG in the arthritic tissue was very similar to that of [18F]FDG. Quantification analysis further showed that [18F]FDG uptake in arthritic tissues at one hour post-injection (p.i.) and Cy5.5-2DG uptakes at different time points p.i. were all well correlated (r2over 0.65). In conclusion, Cy5.5-DG can detect arthritic tissues in living mice. The good correlation between the [18F]FDG uptake and Cy5.5-2DG accumulation in the same arthritic tissue warrants further investigation of Cy5.5-2DG as an approach for assessment of anti-inflammatory treatments.


2011 ◽  
Vol 14 (3) ◽  
pp. 368 ◽  
Author(s):  
Mi-Sook Lee ◽  
Young Han Kim ◽  
Yeon Joo Kim ◽  
Seung-Hae Kwon ◽  
Jeong-kyu Bang ◽  
...  

Purpose TIMP-2 has been studied as an attractive cancer therapeutic candidate, and a TIMP-2 fusion protein (HSA/TIMP-2) displayed effective anticancer activity, despite a lack of information about its pharmacokinetics (PK) and biodistribution. The purpose of this work was to assess the PK and biodistribution of HSA/TIMP-2 as well as to quantify accumulated HSA/TIMP-2 in tumors. Methods Cy5.5 near-infrared (NIR) fluorescence was conjugated to the HSA/TIMP-2 protein (Cy5.5–HSA/TIMP-2) for monitoring spatio-temporal changes in vivo. For PK and biodistribution analysis, 0.2 μg/g body weight of Cy5.5–HSA/TIMP-2 was injected into MAT-LyLu prostate tumor xenografts, which were then imaged using an IVIS-200 optical imaging system. To quantify the accumulated HSA/TIMP-2 in tumors, we introduced a standard curve with depth-corrected fluorescence measurement. Results In the vascular tube formation assay with human umbilical vein endothelial cells (HUVECs), Cy5.5–HSA/TIMP-2 showed an antiangiogenic effect. In prostate cancer xenografts, Cy5.5–HSA/TIMP-2 exhibited a prolongation of blood half-life to 19.6 h and relatively preferential distribution to the tumor. The amount of tumor-accumulated Cy5.5–HSA/TIMP-2 was calculated to be 4.5 ± 0.5 ng/g body weight at 2 days, representing 2.25 ± 0.25% of the initial dose. Conclusions We evaluated the pharmacokinetic profile and biodistribution of HSA/TIMP-2 with favorable results, providing new information for more effective approaches to cancer therapeutics using HSA/TIMP-2. Additionally, real-time in vivo fluorescence imaging analysis using a depth-corrected standard curve may serve as a platform to quantify biodistributed drug in anticancer therapeutic studies. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.


1997 ◽  
Vol 352 (1354) ◽  
pp. 737-742 ◽  
Author(s):  
Mamoru Tamura ◽  
Yoko Hoshi ◽  
Fumihiko Okada

Changes in cerebral blood flow (CBF) and cerebral metabolic rates (CMRO 2 ) have been used as indices for changes in neuronal activity. Near–infrared spectroscopy (NIRS) can also measure cerebral haemodynamics and metabolic changes, enabling the possible use of multichannel recording of NIRS for functional optical imaging of human brain activity. Spatio–temporal variations of brain regions were demonstrated during various mental tasks. Non–synchronous behaviour of cerebral haemodynamics during the neuronsl activation was observed. Gender– and handedness–dependent lateralization of the function between right and left hemispheres was demonstrated by simultaneous measurement using two NIR instruments during the mirror–drawing task. A lack of interhemispheric integration was observed with schizophrenic patients. These observations suggest an application for NIRS in psychiatric disease management, as an addition to clinical monitoring at the bedside. A time–resolved 64–channel optical imaging system was constructed. This consisted of three picosecond laser diodes and 64 channels of TAC and CFD systems. Image reconstruction for phantom model systems was performed. Time–resolved quantitative optical imaging will become real in the very near future.


2021 ◽  
Author(s):  
Ryohei Saito-Moriya ◽  
Rika Obata ◽  
Shojiro A. Maki

The firefly bioluminescence reaction has been exploited for in vivo optical imaging in life sciences. To develop highly sensitive bioluminescence imaging technology, many researchers have synthesized luciferin analogs and luciferase mutants. This chapter first discusses synthetic luciferin analogs and their structure–activity relationships at the luminescence wavelength of the firefly bioluminescence reaction. We then discuss the development of luciferin analogs that produce near-infrared (NIR) light. Since NIR light is highly permeable for biological tissues, NIR luciferin analogs might sensitively detect signals from deep biological tissues such as the brain and lungs. Finally, we introduce two NIR luciferin analogs (TokeOni and seMpai) and a newly developed bioluminescence imaging system (AkaBLI). TokeOni can detect single-cell signals in mouse tissue and luminescence signals from marmoset brain, whereas seMpai can detect breast cancer micro-metastasis. Both reagents are valid for in vivo bioluminescence imaging with high sensitivity.


2020 ◽  
pp. 1-12
Author(s):  
Hailun Zheng ◽  
Mei Zhang ◽  
Xiquan Ke ◽  
Xiaojing Deng ◽  
Dapeng Li ◽  
...  

BACKGROUND: Glycolysis was an essential driver of chemo-resistance in colorectal cancer (CRC), albeit with limited molecular explanations. OBJECTIVE: We strived to elucidate the involvement of lncRNA XIST/miR-137/PKM axis in chemo-tolerance and glycolysis of CRC. METHODS: Altogether 212 pairs of tumor tissues and adjacent normal tissues were collected from CRC patients. Moreover, human CRC epithelial cell lines, including HT29, SW480, SW620 and LoVo, were purchased in advance, and their activity was estimated after transfection of si-XIST or miR-137 mimic. Furthermore, 5-FU/cisplatin-resistance of CRC cells was determined through MTT assay, and glycolytic potential of CRC cells was appraised based on oxygen consumption rate (OCR) and extracellular acidification rate (ECAR). RESULTS: Highly-expressed XIST were predictive of severe symptoms and unfavorable 3-year survival of CRC patients (P< 0.05). Besides, silencing of XIST not only diminished proliferative, migratory and invasive power of CRC cells (P< 0.05), but also enhanced sensitivity of CRC cells responding to 5-FU/cisplatin (P< 0.05). Glycolytic potency of CRC cells was also undermined by si-XIST, with decreased maximal respiration and maximal glycolytic capacity in the si-XIST group as relative to NC group (P< 0.05). Nevertheless, miR-137 mimic attenuated the facilitating effect of pcDNA3.1-XIST on proliferation, migration, invasion, 5-FU/cisplatin-resistance and glycolysis of CRC cells (P< 0.05). Ultimately, ratio of PKM2 mRNA and PKM1 mRNA, despite being up-regulated by pcDNA3.1-XIST, was markedly lowered when miR-137 mimic was co-transfected (P< 0.05). CONCLUSIONS: LncRNA XIST/miR-137 axis reinforced glycolysis and chemo-tolerance of CRC by elevating PKM2/PKM1 ratio, providing an alternative to boost chemo-therapeutic efficacy of CRC patients.


2017 ◽  
Vol 8 (4) ◽  
pp. 2776-2781 ◽  
Author(s):  
Kun Zhang ◽  
Jie Zhang ◽  
Zhen Xi ◽  
Lu-Yuan Li ◽  
Xiangxiang Gu ◽  
...  

A highly sensitive H2S-specific near-infrared fluorescence-enhanced probe was developed for real-time imaging of endogenous H2S in colorectal cancer cells (HCT116 and HT29) in mice.


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