Association between osteogenesis and inflammation during the progression of calcified plaque as evaluated by combined ¹⁸F-NaF and ¹⁸F-FDG PET/CT

Abstract

Background and Aim: ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) is the most widely validated positron emission tomography (PET) tracer for the evaluation of atherosclerotic inflammation. ¹⁸F-sodium fluoride (¹⁸F-NaF) has also been recently considered a potential novel biomarker of osteogenesis in atherosclerosis. We aimed to analyze the association between inflammation and osteogenesis at different stages of atherosclerosis, as well as the interrelationship between these two processes during disease progression. Methods: Thirty-four myeloma patients underwent ¹⁸F-NaF and ¹⁸F-FDG PET/computed tomography (CT) examinations. Three groups (non-calcified; mildly calcified; and severely calcified lesions) were divided based on the calcium density as measured in Hounsfield units (HU) by CT. Tissue-to-background ratios (TBR) were determined from PET for both tracers. The association between inflammation and the osteogenesis during atherosclerosis progression was evaluated in 19 patients who had at least two examinations with both tracers. Results: There were significant correlations between the TBRmax values of the two tracers (Spearman's r = 0.5, P < 0.01, Pearson r = 0.4, P < 0.01) in the 221 lesions at baseline. In non-calcified lesions, highest uptake of both tracers was observed, but without any correlation between both tracers (Pearson r = 0.06, P = 0.76). Compared to non-calcified plaques, concordant significantly lower accumulation was found in mildly calcified plaques, with good correlation between the tracers (Pearson r = 0.7, P < 0.01). In addition, there was enhanced osteogenesis-derived ¹⁸F-NaF uptake, and regressive inflammation-derived ¹⁸F-FDG uptake in severely calcified lesions (Pearson r = 0.4, P < 0.01). During follow-up, there was an increased calcium density and an increased mean ¹⁸F-NaF uptake observed, while the mean ¹⁸F-FDG uptake decreased. The majority of non-calcified (86%) and mildly calcified (81%) lesions and 47% of severely calcified lesions had a concordant development of both vascular inflammation and osteogenesis. Conclusion: The combination of ¹⁸F-NaF and ¹⁸F-FDG PET imaging promotes an understanding of the mechanism of plaque progression, thereby providing new insights into plaque stabilization.