Tomographic fluorescence imaging of tumor vascular volume in mice

Radiology. 2007 Mar;242(3):751-8. doi: 10.1148/radiol.2423052065.


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.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Colonic Neoplasms / blood supply*
  • Colonic Neoplasms / pathology*
  • Image Enhancement / methods*
  • Imaging, Three-Dimensional / methods*
  • Mice
  • Mice, Nude
  • Microscopy, Fluorescence / methods*
  • Neovascularization, Pathologic / pathology*
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Tomography, Optical / methods*