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Detection and Analysis of Tumor Fluorescence Using a Two-Photon Optical Fiber Probe

Thommey P. Thomas ^*, Mon Thiri Myaing , Jing Yong Ye , Kimberly Candido ^*, Alina Kotlyar ^*, James Beals ^*, Peter Cao ^*, Balazs Keszler ^*, Anil K. Patri ^*, Theodore B. Norris  and James R. Baker, Jr. ^*

^* Center for Biologic Nanotechnology, University of Michigan Medical School, Ann Arbor, Michigan; and Center for Ultrafast Optical Science and Electrical Engineering and Computer Science Department, University of Michigan, Ann Arbor, Michigan

Correspondence: Address reprint requests to James R. Baker Jr., E-mail jbakerjr{at}umich.edu.

The utility of a two-photon optical fiber fluorescence probe (TPOFF) for sensing and quantifying tumor fluorescent signals was tested in vivo. Xenograft tumors were developed in athymic mice using MCA207 cells expressing green fluorescent protein (GFP). The TPOFF probe was able to detect ex vivo fluorescence from excised tumors containing as little as 0.3% GFP-expressing cells. TPOFF results were similar to both flow-cytometric analysis of tumor cells after isolation and suspension, and fluorescence determined by microscope images of cryosectioned tumors. TPOFF was then used to measure GFP fluorescence from tumors in live mice. The fiber probe detected fluorescently-labeled Herceptin antibody targeted to HER2-expressing tumors in severe combined immunodeficient mice. Dendrimer nanoparticles targeted by folic acid and having 6-TAMRA as a fluorescent probe were also used to label KB cell tumors in vivo. The fiber probe documented a fourfold increase in tumor fluorescence in animals that received the targeted dendrimer. These results suggest TPOFF can be used as a minimally invasive system for identifying tumor markers and monitoring drug therapy.

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