Assessment of disease activity in rheumatoid arthritis using a novel folate targeted radiopharmaceutical Folatescan

Abstract

Objectives: Development of a simple and accurate technique for detecting active inflammation in the joints and other tissues of patients with inflammatory disorders is an unmet need in rheumatic diseases. This study is a preliminary assessment of the safety and usage of a radiopharmaceutical, FolateScan (Technetium-99m EC20; 99mTc-EC20), for detecting disease activity in patients with rheumatoid arthritis.

Methods: EC20 is a folate-targeted diagnostic radiopharmaceutical which binds to the folate receptor and is preferentially taken up by activated macrophages. In this open-label, cross-sectional study, a total of 40 patients with RA (26 with one or more swollen joints, 14 with clinically quiescent joint disease; 0/66 joint count) as well as 6 patients with osteoarthritis, 12 patients with other inflammatory conditions and 5 healthy subjects received 0.1 mg of EC20 labeled with 20-25mCi of technetium-99m. Disease activity was scored in each joint and other target tissues by a radiologist blinded to the clinical assessment, and results were compared to the rheumatologist's physical examination, which served as the test standard.

Results: The 40 patients (78% female) with RA had a mean age of 56.9 years. Assessment of uptake of 99mTc-EC20 in joints of patients with RA based on image analysis was compared to the clinical examination. FolateScan detected more actively involved joints in 27 patients (68%) than joints recorded as "swollen", and more actively involved joints in 25 patients (63%) than joints recorded as "painful and/or swollen". The number of swollen joints by clinical exam was correlated with ESR (r=0.43; p=0.006) and C-rp (r=0.35; p=0.03). The number of actively involved joints by FolateScan was also correlated with ESR (r=0.47; p=0.002) and C-rp (r=0.36; p=0.02). Joint uptake was also seen in patients with osteoarthritis.

Conclusion: FolateScan is a potentially useful tool for detection of disease activity in patients with RA and may be more sensitive than the physical examination.

Conflict of interest statement

Conflict of interest: Dr. Matteson is a member of the scientific advisory board for inflammatory diseases for Endocyte Inc.; Drs. Low, Messmann and Morgenstern are employees of Endocyte Inc.; the other co-authors have declared no competing interests.

Figures

Fig. 1

Whole body FolateScan of a patient with active rheumatoid arthritis demonstrating increased activity in multiple joints. In addition, there is activity in the parotid glands and salivary glands of the lower jaw. This latter uptake could be suppressed by pretreatment with 1 to 2 mg of iv folate.

Fig. 2

FolateScan in a patient with osteoarthritis of the knees, carpometacarpal joints of the thumbs, and distal interphalangeal joints of the hands, showing no increased uptake in the joints. FolateScan is avidly taken up in the spleen and liver in all subjects.