Next Article in Journal / Special Issue
The Clinical Potential of Circulating Tumor Cells; The Need to Incorporate a Modern “Immunological Cocktail” in the Assay
Previous Article in Journal / Special Issue
Circulating Tumor Cells in Prostate Cancer
Cancers 2013, 5(4), 1691-1738; doi:10.3390/cancers5041691
Review

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

1
 and
1,2,*
1 Phillips Classic Laser and Nanomedicine Laboratories, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205, USA 2 Arkansas Nanomedicine Center, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205, USA
* Author to whom correspondence should be addressed.
Received: 9 September 2013 / Revised: 17 November 2013 / Accepted: 19 November 2013 / Published: 10 December 2013
(This article belongs to the Special Issue Circulating Tumor Cells in Cancers)

Abstract

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-rsesolution PAFC beyond the diffraction and spectral limits.
Keywords: in vivo flow cytometry; metastasis; circulating tumor cells; photoacoustic method; photothermal imaging; CTC assay ex vivo/in vitro in vivo flow cytometry; metastasis; circulating tumor cells; photoacoustic method; photothermal imaging; CTC assay ex vivo/in vitro
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Supplement

Share & Cite This Article

Further Mendeley | CiteULike
Export to BibTeX |
EndNote
MDPI and ACS Style

Galanzha, E.I.; Zharov, V.P. Circulating Tumor Cell Detection and Capture by Photoacoustic Flow Cytometry in Vivo and ex Vivo. Cancers 2013, 5, 1691-1738.

View more citation formats

Related Articles

Article Metrics

For more information on the journal, click here

Comments

Cited By

[Return to top]
Cancers EISSN 2072-6694 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert