Fiber-optic multiphoton flow cytometry in whole blood and in vivo

Chang, Yu‐Chung; Ye, Jing Yong; Thomas, Thommey P.; Cao, Zeyuan; Kotlyar, Alina; Tkaczyk, Eric R.; Baker, James R.; Norris, Theodore B.

doi:10.1117/1.3463481

Cited by 33 publications

(31 citation statements)

References 32 publications

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“…However, the blood volume taken from the patient cannot be sufficiently increased. This apparent conflict could be solved by in vivo detection methods, in which feasibility has been shown (48)(49)(50)(51). An alternative approach is to conduct leukapheresis for CTC isolation (52).…”

Section: Discussionmentioning

confidence: 99%

Challenges in the Enumeration and Phenotyping of CTC

Coumans

Ligthart

Uhr

et al. 2012

Clinical Cancer Research

164

148

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Purpose: Presence of circulating tumor cells (CTC) in metastatic carcinoma is associated with poor survival. Phenotyping and genotyping of CTC may permit "real-time" treatment decisions, provided CTCs are available for examination. Here, we investigate what is needed to detect CTC in all patients.Experimental Design: CTCs enumerated in 7.5 mL of blood together with survival from 836 patients with metastatic breast, colorectal, and prostate cancer were used to predict the CTC concentration in the 42% of these patients in whom no CTCs were found and to establish the relation of concentration of CTCs with survival. Influence of different CTC definitions were investigated by automated cell recognition and a flow cytometric assay without an enrichment or permeabilization step.Results: A log-logistic regression of the log of CTC yielded a good fit to the CTC frequency distribution. Extrapolation of the blood volume to 5 L predicted that 99% of patients had at least one CTC before therapy initiation. Survival of patients with EpCAMþ, cytokeratinþ, CD45À nucleated CTCs is reduced by 6.6 months for each 10-fold CTC increase. Using flow cytometry, the potential three-fold recovery improvement is not sufficient to detect CTC in all patients in 7.5 mL of blood.Conclusions: EpCAMþ, cytokeratinþ, CD45À nucleated CTCs are present in all patients with metastatic breast, prostate, and colorectal cancer and their frequency is proportional to survival. To serve as a liquid biopsy for the majority of patients, a substantial improvement of CTC yield is needed, which can only be achieved by a dramatic increase in sample volume.

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Section: Discussionmentioning

confidence: 99%

Challenges in the Enumeration and Phenotyping of CTC

Coumans

Ligthart

Uhr

et al. 2012

Clinical Cancer Research

164

148

View full text Add to dashboard Cite

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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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“…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%

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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Fiber-optic multiphoton flow cytometry in whole blood and in vivo

Cited by 33 publications

References 32 publications

Challenges in the Enumeration and Phenotyping of CTC

Challenges in the Enumeration and Phenotyping of CTC

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

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