The Purdue team continues to work with the Mayo Clinic and is planning to initiate a clinical trial to further evaluate the technique. The team also plans to develop labels for additional types of cancer and to downsize the equipment to make the technology portable.

This research was funded by an Indiana Elks Charities Grant, the Purdue Cancer Center and an Ovar'Coming Cancer Together research grant.

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Ji-Xin Cheng (foreground), Wei He, Philip Low (left), Haifeng Wang (right)
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A Purdue-led research team developed a new method to detect cancer by scanning surface veins with a laser. Ji-Xin Cheng (foreground), an assistant professor of chemistry and biomedical engineering, and graduate student Wei He, work with the two-photon fluorescence microscope. The microscope is used to detect circulating tumor cells labeled with tumor-specific fluorescent probes developed by Philip Low (left), Purdue's Ralph C. Corley Distinguished Professor of Chemistry. Postdoctoral researcher Haifeng Wang (right) records the data displayed on the computer screen. Low, Cheng, He and Wang co-authored a paper published in the Proceedings of the National Academy of Sciences detailing the cancer detection method and technology. (Purdue News Service photo/David Umberger)

ABSTRACT

In vivo quantitation of rare circulating tumor cells by multiphoton intravital flow cytometry

Wei He, Haifeng Wang, Lynn C. Hartmann, Ji-Xin Cheng, and Philip S. Low

Quantitation of circulating tumor cells (CTCs) constitutes an emerging tool for the diagnosis and staging of cancer, assessment of response to therapy, and evaluation of residual disease after surgery. Unfortunately, no existing technology has the sensitivity to measure the low numbers of tumor cells (<1 CTC per ml of whole blood) that characterize minimal levels of disease. We present a method, intravital flow cytometry, that noninvasively counts rare CTCs in vivo as they flow through the peripheral vasculature. The method involves i.v. injection of a tumor-specific fluorescent ligand followed by multiphoton fluorescence imaging of superficial blood vessels to quantitate the flowing CTCs. Studies in mice with metastatic tumors demonstrate that CTCs can be quantitated weeks before metastatic disease is detected by other means. Analysis of whole blood samples from cancer patients further establishes that human CTCs can be selectively labeled and quantitated when present at 2 CTCs per ml, opening opportunities for earlier assessment of metastatic disease. folate conjugates in vivo imaging multiphoton microscopy metastasis cancer diagnosis

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