Quantitative two-photon flow cytometry—in vitro and in vivo

Zhong, Cheng; Tkaczyk, Eric R.; Thomas, Thommey P.; Ye, Jing Yong; Myc, Andrzej; Bielinska, Anna U.; Cao, Zeyuan; Majoros, István J.; Keszler, B.; Baker, James R.; Norris, Theodore B.

doi:10.1117/1.2931077

Cited by 34 publications

(41 citation statements)

References 34 publications

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“…11 These limitations have motivated the development of noninvasive techniques that can be operated continuously without drawing blood samples. [12][13][14][15][16][17][18][19] Microscopy-based in vivo flow cytometry of fluorescently labeled circulating cells, wherein a laser beam is focused through a microscope objective across a small blood vessel in the ear or retina of a mouse, is one such approach. As cells cross the laser path, a fluorescent pulse is generated that can be detected with a photomultiplier tube (PMT).…”

Section: Introductionmentioning

confidence: 99%

Instrument for fluorescence sensing of circulating cells with diffuse light in mice in vivo

Zettergren¹,

Vickers²,

Runnels

et al. 2012

J. Biomed. Opt.

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Section: Introductionmentioning

confidence: 99%

Instrument for fluorescence sensing of circulating cells with diffuse light in mice in vivo

Zettergren¹,

Vickers²,

Runnels

et al. 2012

J. Biomed. Opt.

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“…One method to enhance the sensitivity is to utilize the multiphoton detection, although with significantly higher cost. Low et al developed a multiphoton intravital flow cytometer to quantify rare circulating tumor cells in vivo and achieved moderately higher sensitivity than confocal detection used in our current in vivo-flow-cytometer (13,(24)(25)(26)(27)(28). Another method is to use the photothermal/ photoacoustic detection, which also improves the detection depth.…”

Section: Discussionmentioning

confidence: 99%

“…The in vivo flow cytometer has the capability to detect and quantify continuously the number and flow characteristics of fluorescently labelled cells in vivo (8)(9)(10)(11)(12)(13)(14)(15). The in vivo flow cytometer allows researchers to acquire cytometric information from the circulation in live animals without extracting blood samples (Fig.…”

mentioning

confidence: 99%

Circulation times of prostate cancer and hepatocellular carcinoma cells by in vivo flow cytometry

Guo

Wang

et al. 2011

Cytometry Pt A

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In metastasis, the cancer cells that travel through the body are capable of establishing new tumors in locations remote from the site of the original disease. To metastasize, a cancer cell must break away from its tumor and invade either the circulatory or lymphatic system, which will carry it to a new location, and establish itself in the new site. Once in the blood stream, the cancer cells now have access to every portion of the body. Here, we have used the ''in vivo flow cytometer'' to study if there is any relationship between metastatic potential and depletion kinetics of circulating tumor cells. The in vivo flow cytometer has the capability to detect and quantify continuously the number and flow characteristics of fluorescently labelled cells in vivo. We have improved the counting algorithm and measured the depletion kinetics of cancer cells with different metastatic potential. Interestingly, more invasive PC-3 prostate cancer cells are depleted faster from the circulation than LNCaP cells. In addition, we have measured the depletion kinetics of two related human hepatocellular carcinoma (liver cancer) cell lines, high-metastatic HCCLM3 cells, and low-metastatic HepG2 cells. More than 60% HCCLM3 cells are depleted within the first hour. Interestingly, the low-metastatic HepG2 cells possess noticeably slower depletion kinetics. In comparison, \40% HepG2 cells are depleted within the first hour. The differences in depletion kinetics might provide insights into early metastasis processes. ' 2011 International Society for Advancement of Cytometry Key terms in vivo flow cytometer; cancer metastasis; circulating tumor cells; prostate cancer; hepatocellular carcinoma; in vivo confocal imaging METASTASIS is a complicated process that has yet to be completely understood. In metastasis, the cancer cells that travel through the body are capable of establishing new tumors in locations remote from the site of the original disease. To metastasize, a cancer cell must break away from its tumor and invade either the circulatory or lymph system (1-3). Once in the blood stream, the cancer cells now have access to every portion of the body. The cancer cells in the bloodstream must fight the body's defense system and try to reattach itself in a new location. Fewer than 1 in 10,000 cancer cells survive circulation to create a new tumor. The circulation of the blood plays an important role in determining where cancer cells travel. The cancer cells usually are trapped in the first set of capillaries that they encounter downstream from their point of entry. These capillaries are often in the lung, since returning deoxygenated venous blood leaving many organs is returned to the lung for reoxygenation. From the intestines, the blood go to the liver first, thus cancer cells leaving the intestines will go there. Therefore, the lung and the liver are the two most common sites for metastasis in the human body. Many circulating cancer cells cannot finish the entire process of metastasis (4).

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“…To monitor CTCs, conventional methods usually isolate and count cells expressing epithelial markers from peripheral blood samples (4)(5)(6)(7)(8)(9)(10). However, these methods are restricted by invasiveness, lower sensitivity caused by small blood sample volumes, and difficulty to record the dynamics of CTCs, which in vivo flow cytometry could overcome (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23). In vivo flow cytometry is optimized to quantify circulating fluorescently labeled cells in live animals, without the need to extract blood samples.…”

Section: Introductionmentioning

confidence: 99%

Real-Time Monitoring of Rare Circulating Hepatocellular Carcinoma Cells in an Orthotopic Model byIn VivoFlow Cytometry Assesses Resection on Metastasis

et al. 2012

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The fate of circulating tumor cells (CTC) is an important determinant of metastasis and recurrence, which leads to most deaths in hepatocellular carcinoma (HCC). Therefore, quantification of CTCs proves to be an emerging tool for diagnosing, stratifying, and monitoring patients with metastatic diseases. In vivo flow cytometry has the capability to monitor the dynamics of fluorescently labeled CTCs continuously and noninvasively. Here, we combine in vivo flow cytometry technique and a GFP-transfected HCC orthotopic metastatic tumor model to monitor CTC dynamics. Our in vivo flow cytometry has approximately 1.8-fold higher sensitivity than whole blood analysis by conventional flow cytometry. We found a significant difference in CTC dynamics between orthotopic and subcutaneous tumor models. We also investigated whether liver resection promotes or restricts hematogenous metastasis in advanced HCC. Our results show that the number of CTCs and early metastases decreases significantly after the resection. The resection prominently restricts hematogenous metastasis and distant metastases. CTC dynamics is correlated with tumor growth in our orthotopic tumor model. The number and size of distant metastases correspond to CTC dynamics. The novel in vivo flow cytometry technique combined with orthotopic tumor models might provide insights to tumor hematogenous metastasis and guidance to cancer therapy. Cancer Res; 72(10); 2683-91. Ó2012 AACR.

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Quantitative two-photon flow cytometry—in vitro and in vivo

Cited by 34 publications

References 34 publications

Instrument for fluorescence sensing of circulating cells with diffuse light in mice in vivo

Instrument for fluorescence sensing of circulating cells with diffuse light in mice in vivo

Circulation times of prostate cancer and hepatocellular carcinoma cells by in vivo flow cytometry

Real-Time Monitoring of Rare Circulating Hepatocellular Carcinoma Cells in an Orthotopic Model byIn VivoFlow Cytometry Assesses Resection on Metastasis

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