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Experimental Studies |
1 From the Department of Radiology, Center for Molecular Imaging Research, CNY149-5403, Massachusetts General Hospital, 13th St, Boston, MA 02125. From the 1998 RSNA scientific assembly. Received January 8, 1999; revision requested March 5; revision received March 26; accepted July 1. Supported in part by a faculty award grant from the Center for Innovative Minimally Invasive Therapy. Address reprint requests to R.W. (e-mail: weissleder@helix.mgh.harvard.edu).
PURPOSE: To build and test an optical imaging system that is sensitive to near-infrared fluorescent molecular probes activated by specific enzymes in tumor tissues in mice.
MATERIALS AND METHODS: The imaging system consisted of a source that delivered 610–650-nm excitation light within a lighttight chamber, a 700-nm longpass filter for selecting near-infrared fluorescence emission photons from tissues, and a charge-coupled device (CCD) for recording images. The molecular probe was a biocompatible autoquenched near-infrared fluorescent compound that was activated by tumor-associated proteases for cathepsins B and H. Imaging experiments were performed 0–72 hours after intravenous injection of the probe in nude mice that bore human breast carcinoma (BT-20).
RESULTS: The imaging system had a maximal spatial resolution of 60 µm, with a field of view of 14 cm2. The detection threshold of the nonquenched near-infrared fluorescent dye was subpicomolar in the imaging phantom experiments. In tissue, 250 pmol of fluorochrome was easily detected during the 10-second image acquisition. After intravenous injection of the probe into the tumor-bearing animals, tumors as small as 1 mm became detectable because of tumor-associated enzymatic activation of the quenched compound.
CONCLUSION: Tumor proteases can be used as molecular targets, allowing visualization of millimeter-sized tumors. The development of this technology, probe design, and optical imaging systems hold promise for molecular imaging, cancer detection, and evaluation of treatment.
Index terms: Animals • Breast neoplasms, experimental studies, 00.32 • Contrast media, experimental studies • Enzymes • Neoplasms, diagnosis, 00.32 • Neoplasms, experimental studies, 00.32
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