Towards <i>in vivo</i> flow cytometry

Tuchin, Valery V.; Tárnok, Attila; Zharov, Vladimir P.; Editors, Guest

doi:10.1002/jbio.200910546

Cited by 13 publications

(9 citation statements)

References 15 publications

(12 reference statements)

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“…In addition, invasive extraction of blood from a living organism may alter CTC parameters (e.g., signaling, epigenetic states, metabolic activities, or morphology) and prevent the long-term study of CTC properties (e.g., CTC-blood cell interactions, aggregation, rolling, or adhesion) in their natural biological environment. These problems can be solved by assessing a significantly larger volume of blood up to a patient’s entire blood volume with in vivo FC, whose principles were proposed in 2004 simultaneously by Zharov and other groups [ 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 ].…”

Section: Introductionmentioning

confidence: 99%

Circulating Tumor Cell Detection and Capture by Photoacoustic Flow Cytometry in Vivo and ex Vivo

Galanzha

Zharov

2013

Cancers

108

137

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Despite progress in detecting circulating tumor cells (CTCs), existing assays still have low sensitivity (1–10 CTC/mL) due to the small volume of blood samples (5–10 mL). Consequently, they can miss up to 103–104 CTCs, resulting in the development of barely treatable metastasis. Here we analyze a new concept of in vivo CTC detection with enhanced sensitivity (up to 102–103 times) by the examination of the entire blood volume in vivo (5 L in adults). We focus on in vivo photoacoustic (PA) flow cytometry (PAFC) of CTCs using label-free or targeted detection, photoswitchable nanoparticles with ultrasharp PA resonances, magnetic trapping with fiber-magnetic-PA probes, optical clearance, real-time spectral identification, nonlinear signal amplification, and the integration with PAFC in vitro. We demonstrate PAFC’s capability to detect rare leukemia, squamous carcinoma, melanoma, and bulk and stem breast CTCs and its clusters in preclinical animal models in blood, lymph, bone, and cerebrospinal fluid, as well as the release of CTCs from primary tumors triggered by palpation, biopsy or surgery, increasing the risk of metastasis. CTC lifetime as a balance between intravasation and extravasation rates was in the range of 0.5–4 h depending on a CTC metastatic potential. We introduced theranostics of CTCs as an integration of nanobubble-enhanced PA diagnosis, photothermal therapy, and feedback through CTC counting. In vivo data were verified with in vitro PAFC demonstrating a higher sensitivity (1 CTC/40 mL) and throughput (up to 10 mL/min) than conventional assays. Further developments include detection of circulating cancer-associated microparticles, and super-resolution PAFC beyond the diffraction and spectral limits.

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Section: Introductionmentioning

confidence: 99%

Circulating Tumor Cell Detection and Capture by Photoacoustic Flow Cytometry in Vivo and ex Vivo

Galanzha

Zharov

2013

Cancers

108

137

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“…Indeed, in conventional FCM in the small volume of blood extracted (typically a few milliliters), no less than one abnormal cell (e.g., CTC or bacteria) can be detected. As a result, its current sensitivity level of 1–10 cells/mL is equivalent to 5,000–50,000 cells in the entire volume of blood (∼5 L in adult), which is sufficient for the rapid development of a disease to a stage that is barely treatable or is incurable, that is, metastasis, septic shock, or sickle cell crisis (15–18). These shortcomings can be solved by development of a FCM instrument that allows in vivo noninvasive, continuous assessment of a significantly larger blood volume than current instruments detect and potentially a patient's entire blood volume (15).…”

mentioning

confidence: 99%

“…FCM is the general term for quantitative detection, identification and enumeration of individual cells in flow (2, 5, 18). A significant contribution in development of in vivo FCM for single cell analysis directly in the blood flow was made since 2004 by Vladimir Zharov's group in the University of Arkansas for Medical Sciences (15, 19–42) and Charles Lin's team in the Wellman Center for photomedicine at Massachusetts General Hospital (43–57) using photothermal [PT]‐based (e.g., thermal lens and photoacoustic [PA]) and fluorescent methods, respectively.…”

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confidence: 99%

In vivo flow cytometry: A horizon of opportunities

2011

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Flow cytometry has been a fundamental tool of biological discovery for many years. Invasive extraction of cells from a living organism, however, may lead to changes in cell properties and prevents studying cells in their native environment. These problems can be overcome by use of in vivo flow cytometry which provides detection and imaging of circulating normal and abnormal cells directlyin blood or lymph flow. The goal of this mini-review is to provide a brief history, features and challenges of this new generation of flow cytometry methods and instruments. Spectrum of possibilities of in vivo flow cytometry in biological science (e.g., cell metabolism, immune function, or apoptosis) and medical fields (e.g., cancer, infection, cardiovascular disorder) including integrated photoacoustic-photothermal theranostics of circulating abnormal cells are discussed with focus on recent advances of this new platform.

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“…Furthermore, we sought to assess the possible use of CTC indices as markers of primary tumor treatment efficacy and whether or not certain vascular damaging therapies had distinguishable effects on CTC levels or correlated to metastatic progression. An in vivo flow cytometry method for real time CTC quantification developed by our group 10,15 provided an opportunity to reveal short term (within minutes) as well as enumerate at later dates a snapshot of CTCs after radiation or anti-vascular treatment. Prior to initiating the study described herein, an initial study was conducted to ascertain if CTCs are released following CYT-6091 therapy in a translational model.…”

Section: Introductionmentioning

confidence: 99%

Real-time monitoring of circulating tumor cell (CTC) release after nanodrug or tumor radiotherapy using in vivo flow cytometry

Koonce

Juratli

Cai

et al. 2017

Biochemical and Biophysical Research Communications

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Noninvasive biological readouts of tumor metastatic risk and therapeutic efficacy are needed as healthcare costs rise. Conventional imaging modalities are expensive; require significant periods of time to see appreciable change and repetitive use increases risk of hazardous side effects. Utilizing circulating tumor cells (CTCs) as a minimally invasive biological readout of tumor progression or therapeutic response is increasingly being studied. While focus has primarily been on the predictive value of naturally occurring CTCs, a more recent effort has emerged regarding the potential consequence of therapy induced CTCs. Here we report an investigation on the acute and long-term effect of vascular disrupting therapies (high-dose radiotherapy and tumor necrosis factor-alpha (TNF)) on CTCs monitored with a non-invasive real-time system. Acute mobilization of CTCs into the blood following both radiation and TNF treatment was observed. There was no increase in metastasis frequency or extent between control and TNF-treated mice; however, a significant reduction in lung metastasis was noted in the radiotherapy alone group. Mice treated with both TNF and radiotherapy had a slightly elevated metastatic profile between that of radiation alone and control (untreated) tumors. Possible mechanisms based on therapy specific vessel disruption and cell death are discussed. Overall, CTCs correlated with tumor progression and suggest CTC enumeration described herein may be useful in clinical management of solid tumor malignancies.

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Towards in vivo flow cytometry

Cited by 13 publications

References 15 publications

Circulating Tumor Cell Detection and Capture by Photoacoustic Flow Cytometry in Vivo and ex Vivo

Circulating Tumor Cell Detection and Capture by Photoacoustic Flow Cytometry in Vivo and ex Vivo

In vivo flow cytometry: A horizon of opportunities

Real-time monitoring of circulating tumor cell (CTC) release after nanodrug or tumor radiotherapy using in vivo flow cytometry

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