Fluorescence imaging depicts macrophages associated with early rheumatoid arthritis

CONTEXT: Researchers at the Institute of Diagnostic and Interventional Radiology at the University of Jena, Germany, are investigating a relatively cheap and simple method for detecting and monitoring rheumatoid arthritis. They hope that near-infrared fluorescence imaging (NIRF) will highlight pathological changes associated with the degenerative joint condition. Initial experiments in mice indicate the technique's promise as an alternative to more complex, specific targeting methods for visualizing early signs of arthritic involvement.

RESULTS: Antigens were used to induce arthritis in one knee in each of nine mice. NIRF was performed on the mice to gain baseline readings. Seven days later, the animals received an intravenous dose of the native fluorochrome Cy5.5, which absorbs and re-emits light in the near-infrared region. The team repeated the NIRF procedure up to 72 hours after injection, recording signal intensities from the arthritic and nonarthritic knee joints in arbitrary units (au).

The NIRF results, presented at a scientific session on molecular imaging at this year's European Congress of Radiology, showed significant accumulation of Cy5.5 in each animal's arthritic knee and a much smaller accumulation of dye in the contralateral knee. The mean signal intensities two hours after fluorochrome administration for the arthritic and normal joints were 1372 au (+208) and 828.4 au (+184.7), respectively. Laboratory analysis confirmed the reason for dye accumulation as intracellular incorporation within macrophages, an early sign of arthritis.

IMAGE: NIRF following injection of fluorochrome dye in mouse shows strong fluorescence signal emitted from arthritic joints. A much weaker signal was observed from nonarthritic joints. (Reprinted with permission of Wiley Interscience)

IMPLICATIONS: "The presence of macrophages is an earlier sign than those you see on x-ray or MRI," said Dr. Ingrid Hilger, head of experimental radiology at the University of Jena, and coauthor of the study. "We could see a huge difference between the arthritic and nonarthritic joints, even though our control joints showed a slight fluorescence too."

Fluorochrome imaging offers results comparable to antibody imaging or use of "intelligent" dyes when assessing macrophage presence, Hilger said. It has the added advantage of being simpler and cheaper. Specific targeting methods are likely to have the edge over NIRF when visualizing other known arthritis markers such as those in the synovial membrane, she said.