FR expressed on activated macrophages in patients with rheumatoid arthritis can be exploited to deliver folate-conjugated imaging agents to inflamed joints. (A) Synovial cells from 4 patients with rheumatoid arthritis were labeled with anti-CD11b to stain human macrophages and then incubated with folate-FITC in the absence (left panel) and presence (right panel) of 100-fold excess free folic acid before examination by flow cytometry. A representative flow plot is shown here. (B) Radioimage of the hands (left) and feet (right) of a patient with active rheumatoid arthritis, showing sites of uptake of EC20, a folate-targeted ^99mTc-based radioimaging agent, in multiple joints of the hands and feet. (C) Radio-image with EC20 of the hands (left) and feet (right) of a nonarthritic patient obtained under identical conditions to those shown in panel B.