⁶⁴Cu-ATSM and ^99mTc(CO)₃-DCM20 potential in the early detection of rheumatoid arthritis

Abstract

Objectives

Molecular imaging constitutes a promising technique for the early detection of rheumatoid arthritis (RA). Macrophages and hypoxia play significant roles in inflamed synovium. In the present study, we evaluated the efficacy of radiopharmaceuticals that target macrophage mannose receptors (^99mTc-labeled mannosylated dextran or ^99mTc(CO)₃-DCM20) and hypoxia (copper(II) diacetyl-di(N⁴-methylthiosemicarbazone) or Cu-ATSM) for the early detection of RA in collagen-induced arthritis (CIA) mice models.

Methods

CIA model was developed in DBA/1 mice, and the clinical score for arthritis was visually assessed on a regular basis. Two biodistribution studies were performed in a paired-labeled format using 2-deoxy-2-¹⁸F-fluoro-D-glucose (¹⁸F-FDG) as a reference: (1) ^99mTc(CO)₃-DCM20 with ¹⁸F-FDG and (2) ⁶⁷Cu-ATSM with ¹⁸F-FDG.

Results

The accumulation levels of ^99mTc(CO)₃-DCM20 and ⁶⁷Cu-ATSM in forepaws, hindpaws, and knee joints of CIA mice were significantly higher than that of control mice. In contrast, ¹⁸F-FDG uptake in hindpaws and knee joints showed no significant difference between CIA and control mice. The radioactivity levels of ^99mTc(CO)₃-DCM20 and ⁶⁷Cu-ATSM were significantly correlated with the clinical scores for the paws.

Conclusion

These results suggest the potential usefulness of ^99mTc(CO)₃-DCM20 and radiolabeled Cu-ATSM for the imaging and early detection of RA.

Keywords:

• Early detection
• hypoxia
• macrophage mannose receptor
• molecular imaging
• rheumatoid arthritis

Acknowledgments

We thank Mr. Takashi Ogasawara (Cyclotron Facility, Gunma University Hospital) for producing the ¹⁸F-FDG.

Conflict of interest

None.