Anti-TNF-α in Pet Imagery: A Non-Invasive Tool to Personalize Diagnosis and Treatments Against Inflammatory Diseases

Objectives Rheumatoid arthritis (RA) is the most prevalent form of immune mediated inflammatory arthritis. It affects close to 1% of Canadian.[1] DMARD therapies are currently guided by a trial-and-error approach to identify the most suitable treatment for each patient. Despite the fast evolution and the high number of available therapy options, the management of rheumatoid symptoms is still challenging. Approximately 30-40% of RA patients do not respond to the first-line treatment.[2] This trial-and-error strategy allows disease progression and may lead to irreversible joint damage due to sustained inflammation. These permanent changes directly affect patients’ well-being and autonomy, ultimately increasing healthcare costs for society. The TNF-α is an inflammation mediator and a key player in inflammatory diseases such as rheumatoid arthritis.[3] TNF-α is found in 50-70 % of RA patients at elevated level in synovial tissues. A phase III clinical trial previously demonstrated that adalimumab, an anti-TNF-α monoclonal antibody, elicited a strong therapeutic response in approximately 60% of RA patients (ACR20).[3] Based on this observation, we postulate that adalimumab could be used to develop an imagery technique to identify patients with the higher level of TNF-α. This tool could be a game changer to pursue personalized therapy and avoid unnecessary therapeutics. Methods In this study we proposed to conjugate a commercial anti-TNF-α antibody (Yuflima, containing adalimumab; Celltrion) with a radiomaker 89 zirconium coupled with a DFO chelator. The 89Zr-DFO-Adalumimab will be used in PET (positron emission tomography) imagery to identify RA patients expressing elevated level of TNf-α in the joint. Results We successfully conjugated the radiomarker Zirconium 89 to the Adalumimab antibody. Preliminary results show that the conjugate DFO-Adalumimab is still able to target TNF-α with the same affinity as the commercial adalimumab. Conclusion These promising findings will enable us to test 89Zr-DFO-adalimumab in a collagen-induced arthritis (CIA) mouse model (DBA/1 strain) to assess inflammation at the join levels using PET imaging. References [1.] Government of Canada. https://www.canada.ca/en/public-health/services/publications/diseases-conditions/rheumatoid-arthritis.html [2.] Babaahmadi M. Stem Cell Res Ther 2023;14:268. [3.] Wang Z. Front Immunol 2021;12:755844.