Total Body PET/CT Imaging Biomarkers for Diagnosing and Quantifying Inflammatory Burden of Psoriatic Arthritis
Principal Investigator: Siba Raychaudhuri, M.D.
Institution: University of California, Davis
Grant Mechanism: R01 Bridge Grant
Funding Amount: $100,000
Project Start Date: February 1, 2022
Project End Date: January 31, 2023
Keywords: Psoriatic Arthritis, Biomarkers, Immunology
There are no diagnostic tests for psoriatic arthritis (PsA). PsA may cause permanent joint damages if left without treatment even for a period of 6 months. Thus, there is a need for a diagnostic test for PsA at an early stage of the disease.
In this proposal we are developing a diagnostic test for PsA by a new method called total body (TB) positron emission tomography (PET) and X-ray computed tomography (CT) scanning. This TB-PET/CT scan:
- Allows whole body examination including all joints of the body
- Identifies inflammation in the body at an early stage
To date, we have studied about 60 study subjects. Our results are very promising and suggest that with the TB-PET/CT scan we can identify the damage of the joints, bones and ligaments which are specific for PsA. This data requires to be substantiated in a larger number of patients. Here we will study 50 more subjects and this will establish that a single TB-PET/CT scan will be able to diagnose PsA. This test can also identify the severity of PsA, and underlying heart and liver diseases of PsA. We intend to extend our research work further to develop and upgrade this diagnostic test.
How will your project help improve the lives of the 125 million affected by psoriatic disease?
About 30% of patients with psoriasis may develop PsA. PsA may cause permanent joint damages if left without treatment even for a period of 6 months. Thus, a prompt diagnosis and management of PsA is critical for reducing the risk of permanent joint/ligament damage and disabilities.
However, current clinical evaluation of PsA primarily relies on a physical exam, which is subjective and lacks sensitivity. It is also not comprehensive – there are 6 clinical domains unique to PsA, namely, arthritis of the large and small joints, enthesitis, dactylitis, axial disease, and nail and skin pathology that must be evaluated. However, there are limitations to access/asses all these and physically palpate these anatomical domains. As a result, PsA remains undiagnosed, or diagnosis gets delayed.
The objective of our study is to identify and quantify the degree of inflammation and structural damage from TB-PET/CT imaging and correlate with the five clinical domains of PsA (arthritis, enthesitis, dactylitis, spinal and nail inflammation).
Total Body PET/CT imaging as proposed in this project identifies and provides quantitative indices of degree of inflammatory changes earlier than the appearance of clinical features; thus, this diagnostic tool has the potential to identify PsA at its initiation that is diagnosing PsA at its transition from psoriasis.
Why is psoriatic disease research important to you, personally? What role will this award play in your research efforts or career development?
Psoriatic arthritis (PsA) is a chronic, systemic, autoimmune disorder that results in significant functional disability and musculoskeletal pain. Delayed PsA treatment by even a few months may cause permanent joint and entheseal damage. Effective treatments for targeting PsA continue to advance, however, early assessment of disease activity for guiding treatment selection and rapid initiation of treatment are critical as they improve long-term outcomes, with remission as a realistic goal. Current clinical assessment primarily relies on a physical exam, which is subjective and has poor sensitivity for evaluating early PsA disease activity and monitoring treatment response. PsA presentation may be heterogeneous and not accompanied by skin psoriasis, and its consequence on impacted tissues may be occult or inaccessible for current methods. There is therefore a pressing need for improved clinical tools to evaluate PsA early to guide treatment selection and monitor treatment response. This need is magnified since elevated PsA disease activity is a known risk factor for other adverse disorders, including cardiovascular and metabolic disease.
TB-PET-CT, being a very sensitive tool, is able to pick and quantify inflammation at any time point of the disease process of PsA, as demonstrated in our preliminary data. Thus, the TB-PET/CT will not only provide the diagnosis of PsA, and beyond that a detailed quantification of the degree of total systemic inflammatory burden in PsA, a quantitative measure for the severity of the disease; and as well subclinical/clinical involvement of the 5 domains. TB-PET-CT imaging will be also able to identify therapeutic response or failure much earlier than the apparent clinical changes identified by currently existing clinical measures.
Dr. Siba Raychaudhuri is a rheumatologist, dermatologist, and immunologist and will be working closely with Drs. Tartar and Hwang in the Rheumatology-Dermatology multidisciplinary clinic. Dr. Raychaudhuri has appointments at both the VA Sacramento Medical Center (VAMC) and UC Davis, where he is the Director of the Rheumatology & Immunology Training Fellowship program. Dr. Raychaudhuri teaches clinical immunology and autoimmune disease to medical students, immunology graduate students, and residents. At the Stanford University Medical Center, Dr. Raychaudhuri directed a very successful psoriasis research program utilizing cutting-edge therapies for autoimmune disease. He has now established the Psoriasis Research Center at the VAMC.