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Introduction Calcinosis affects a significant proportion of patients with systemic sclerosis (SSc) and substantially compromises quality of life due to associated pain, ulceration, soft tissue infection and dysfunction. The varying severity and progression of calcinosis among patients remain poorly understood. Traditional imaging methods cannot assess metabolic activity, thus have limited utility in predicting prognosis. This study evaluates the effectiveness of 18F-NaF PET/CT in diagnosing, monitoring, and predicting subcutaneous calcinosis progression in SSc patients.Material and Methods A 12-month prospective study was conducted in 27 SSc patients (26 female, 1 male). Comprehensive demographic and clinical data were collected. Patients underwent physical examinations at regular intervals (0, 3, 6, and 12 months), with calcinosis nodules measured and complications documented. Patient-reported outcome measures, including the Scleroderma Health Assessment Questionnaire (SHAQ) and Mawdsley Calcinosis Questionnaire were administered. Whole-body 18F-NaF PET/CT scans were performed at baseline and study completion, analyzing presence, size, density (Hounsfield Units [HU]), and metabolic activity (Standardized Uptake Value [SUV]) of lesions. A segmentation approach was employed to assess mean HU and SUV values when spatial resolution limited single lesion delineation.Results Mean age of the patients was 58.3±12.9 years with average disease duration of 117.9±120 months and mean modified Rodnan Skin Score (mRSS) of 8.93±8.81. Fourteen patients had limited cutaneous SSc. Antibody profiles included: ACA 13/27, ATA 9/27, ARA 3/27, negative 3/27. At baseline, 95 nodules were identified clinically across 64 anatomical regions (based on mRSS assessment areas) while PET/CT identified 97 solitary lesions (HUmax: 1357.8±501.1; SUVmax 7.46±6.02) and 24 conglomerates of non-measurable lesions across 136 regions. Visual grading differentiated 18F-NaF avid from non-avid lesions. Of the 24 patients who completed the study, 21 underwent a second PET/CT scan. At follow-up, 11 new lesions with moderate to high metabolic activity were detected by PET/CT. Physical examination of this subgroup revealed that 13 nodules had resolved, while 27 new nodules had developed. Complications (fistula, ulceration, or inflammation) were observed in 23 nodules in 11 patients over the 1-year study period.Conclusions 18F-NaF PET/CT is a promising method for visualizing subcutaneous calcinosis. Its low-dose CT component demonstrates calcification, while tracer uptake provides information on metabolic activity. Importantly, it identifies far more lesions than physical examination, including those in unusual locations or deeper tissues. Given the high avidity of newly formed lesions, high metabolic activity may serve as a prognostic marker for disease progression.Abstract P.239 Figure 1