In vivo imaging and quantitation of rare circulating tumor cells

ANYL 53

Wei He, He11@purdue.edu1, Haifeng Wang, wangh@ecn.purdue.edu2, Lynn C. Hartmann3, Ji-Xin Cheng, jcheng@purdue.edu4, and Philip S. Low1. (1) Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, IN 47907, (2) Department of Biomedical Engineering, Purdue University, 206 S. Intramural Drive, West Lafayette, IN 47907, (3) Division of Medical Oncology, Mayo Clinic, Rochester, MN 55905, (4) Weldon School of Biomedical Engineering, Purdue Univerisity, 206 South Intramural Drive, West Lafayette, IN 47907
Circulating tumor cells (CTCs) disseminated from primary tumor into blood circulation constitute a major factor for pathogenesis of distant metastasis. Thus, the ability to detect and quantitate CTCs can be a powerful tool for the diagnosis and staging of cancer, assessment of response to therapy, and evaluation of residual disease after surgery. Unfortunately, existing technologies for CTC assessment are all in vitro assays, and yet reach reliable sensitivity to measure the low numbers of CTCs (<1 CTC/ml blood) in early cancer development or after tumor resection surgery. Here we present an in vivo method that can noninvasively image and quantitate rare CTCs as they flow through the peripheral vasculature. The method involves intravenous injection of a CTC-specific fluorescent ligand followed by multiphoton fluorescence imaging of superficial blood vessels to quantitate the flowing CTCs. Compared to in vitro assays, this method can increase the sampling volume of peripheral blood in cancer patients to make the measurement statistically significant. Studies in mice with metastatic tumors demonstrate that CTCs can be quantitated two weeks before metastatic disease is detected by conventional technologies, including histology/pathology, immunohistochemistry and confocal fluorescence microscopy. Analysis of peripheral blood samples from cancer patients further establishes that human CTCs can be selectively labeled by our fluorescent probes in multiple cancer types, opening opportunities for ultra-sensitive, real-time and non-invasive diagnosis of metastatic disease in vivo.
 

General Posters
7:00 PM-9:00 PM, Sunday, August 19, 2007 BCEC -- Exhibit Hall - B2, Poster

Division of Analytical Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007