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

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

Research output: Contribution to journalArticlepeer-review

235 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)11760-11765
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number28
StatePublished - Jul 10 2007


  • Cancer diagnosis
  • Folate conjugates
  • In vivo imaging
  • Metastasis
  • Multiphoton microscopy

ASJC Scopus subject areas

  • General


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