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Tomographic Fluorescence Imaging of Tumor Vascular Volume in Mice¹

¹ From the Center for Molecular Imaging Research, Massachusetts General Hospital and Harvard Medical School, Building 149, 13th St, Room 5403, Charlestown, MA 02129. Received December 19, 2005; revision requested February 10, 2006; revision received March 22; accepted April 19; final version accepted July 6. R.W. supported in part by P50 CA86355, P01 CA69246, R24 CA92782, and R33 CA91807 grant. X.M. supported by the Swiss National Science Foundation. Address correspondence to R.W. (e-mail: weissleder{at}helix.mgh.harvard.edu).

Purpose: To prospectively determine the feasibility of imaging vascular volume fraction (VVF) and its therapeutic inhibition in mouse models of cancer with three-dimensional fluorescence molecular tomography (FMT).

Materials and Methods: All studies were approved by the institutional animal review committee and were in accordance with National Institutes of Health guidelines. CT26 colon tumor–bearing mice were imaged with FMT after intravenous administration of long-circulating near-infrared fluorescent blood-pool agents optimized for two nonoverlapping excitation wavelengths (680 and 750 nm). A total of 58 mice were used for imaging VVF to evaluate the following: (a) differences in ectopically and orthotopically implanted tumors (n = 10), (b) cohorts of mice (n = 24) treated with anti–vascular endothelial growth factor (VEGF) antibody, (c) serial imaging in same animal to determine natural course of angiogenesis (n = 4), and (d) dose response to anti-VEGF therapy (n = 20). To compare groups receiving antiangiogenic chemotherapy, analysis of variance was used.

Results: Fluorochrome concentrations derived from FMT measurements were reconstructed with an accuracy of ±10% at 680 nm and ±7% at 750 nm and in a depth-independent manner, unlike at reflectance imaging. FMT measurements of vascular fluorescent probes were linear, with concentration over several orders of magnitude (r > 0.98). VVFs of colonic tumors, which varied considerably among animals (3.5% ± 1.5 [standard deviation]), could be depicted with in vivo imaging in three dimensions with less than 5 minutes of imaging and less than 3 minutes of analysis. The natural course of angiogenesis and its inhibition could be reliably imaged and depicted serially in different experimental setups.

Conclusion: FMT is a tomographic optical imaging technique that, in conjunction with appropriate fluorescent probes, allows quantitative visualization of biologic processes.

© RSNA, 2007

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