AB0726 CAN DEPLETION OF FAPα SYNOVIAL FIBROBLASTS LEAD TO AMELIORATION OF INFLAMMATORY ARTHRITIS?

Background:

Fibroblast activation protein α (FAPα) is a cell surface serine protease expressed by activated fibroblasts, and it was found that FAP-deficiency mice have less cartilage degradation, inflammation, and bone erosion. Moreover, the fibroblast-like synoviocytes from rheumatoid arthritis patients have higher expression of FAPα in synovium tissue.

Objectives:

We evaluated the ability of the ⁶⁸Ga-labelled FAPI as a diagnostic method for RA diagnosis. We also investigated that ¹⁷⁷Lu-labelled FAPI could lead to amelioration of RA by depletion of FAP⁺ FLS and subsequent inhibition of lymphocyte function.

Methods:

The collagen-induced arthritis (CIA) DBA1/J mice were used as the inflammatory arthritis model. The images from ⁶⁸Ga-FAPI-04 PET/CT examinations of CIA mice were analyzed, and the tracer uptakes would be quantified by the standardized uptake value (SUV) and compared with the disease score and incidence rate. Then ¹⁷⁷Lu-labeled FAPI-04 was used to target FAPα-expressed cells in CIA mice as radiation therapy.

Results:

The paws in CIA mice with higher SUV since 1 week after booster immunization had a higher incidence rate of arthritis. The SUV also correlated with arthritis scores because the expression of FAPα increased in CIA mice. Moreover, the ¹⁷⁷Lu-labeled FAPI-04 treated group has a lower arthritis score compared with untreated CIA mice.

Conclusion:

We provide the basic features of FAPα- expressed FLSs in RA pathophysiology and advances in targeted therapies. We present that Ga⁶⁸-FAPI-04 can be a useful tracer for predicting arthritis, and targeting to FAPα- expressed FLSs may be a potential way for arthritis treatment.

REFERENCES:

NIL.

Acknowledgements:

This work was supported by grants from the Keelung Chang Gung Memorial Hospital, Taiwan, R.O.C. (CMRPG2K0172 and CMRPG2K0173) and NSTC-Granted Research Projects (NSTC 112-2314-B-182 -015 -MY3).

Disclosure of Interests:

None declared.