Fluorescence tomography quantifies tumor response to chemotherapy

CONTEXT: To more precisely gauge tumor reaction to chemotherapy in small animals, researchers at the Center for Molecular Imaging Research at Massachusetts General Hospital, Harvard Medical School are investigating the effectiveness of fluorescence molecular tomography (FMT) compared with the more commonly used planar illumination. In a study led by Dr. Vasilis Ntziachristos, an assistant professor of bioengineering, in vivo imaging using 3D FMT demonstrated superior quantification, resolution, and more accurate depth and size information than 2D planar imaging.

RESULTS: Thirteen mice were injected in the left mammary pad with Lewis lung carcinoma (LLC) cells and then with cyclophosphamide-resistant LLC cells in the right mammary pad. Eight days later, 10 animals received an injection of cyclophosphamide. To obtain fluorescent images, mice were injected with Annexin V tagged with a cyanine dye (Cy5.5-Annexin V), a phosphatidylserine-sensing fluorescent probe. Two hours after the probe injection, animals were imaged on a prototype scanner combining planar imaging and FMT. Imaging revealed that fluorochrome concentration increased 10-fold in cyclophosphamide-sensitive tumors and seven-fold in resistant tumors, compared with control groups. While FMT showed consistent quantitative results, planar imaging results varied. FMT was less sensitive than planar imaging to background fluctuations and corrected for attenuation changes as a function of depth.

IMAGE: A planar image (above) corresponds with an FMT slice of a tumor demonstrating uptake of the Annexin V-tagged agents at a depth of 1.3 cm. Uptake patterns from the 0.8-mm slices offer quantitative measures of response to cyclophosphaide therapy. (Image reprinted with permission of Proceedings of National Academy of Sciences)

IMPLICATIONS: FMT has proven very accurate for noninvasive imaging of molecular processes in vivo.

"This optical technology is essential for biomedical research involving small animals and has potential for clinical transferability as well," Ntziachristos said.

The researchers are evaluating ways to further enhance FMT imaging performance by refining their understanding of the physical principles that make FMT possible and developing better hardware to more fully exploit its imaging potential.