Association Between Osteogenesis and Inflammation During the Progression of Calcified Plaque Evaluated by ¹⁸F-Fluoride and ¹⁸F-FDG

Abstract

18 F-FDG is the most widely validated PET tracer for the evaluation of atherosclerotic inflammation. Recently, 18 F-NaF has also been 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 2 processes during disease progression. Methods: Thirty-four myeloma patients underwent 18 F-NaF and 18 F-FDG PET/CT examinations. Lesions were divided into 3 groups (noncalcified, mildly calcified, and severely calcified lesions) on the basis of calcium density as measured in Hounsfield units by CT. Tissue-to-background ratios were determined from PET for both tracers. The association between inflammation and osteogenesis during atherosclerosis progression was evaluated in 19 patients who had at least 2 examinations with both tracers. Results: There were significant correlations between the maximum tissue-to-background ratios of the 2 tracers (Spearman r 5 0.5 [P , 0.01]; Pearson r 5 0.4 [P , 0.01]) in the 221 lesions at baseline. The highest uptake of both tracers was observed in noncalcified lesions, but without any correlation between the tracers (Pearson r 5 0.06; P 5 0.76). Compared with noncalcified plaques, mildly calcified plaques showed concordant significantly lower accumulation, with good correlation between the tracers (Pearson r 5 0.7; P , 0.01). In addition, enhanced osteogenesis-derived 18 F-NaF uptake and regressive inflammation-derived 18 F-FDG uptake were observed in severely calcified lesions (Pearson r 5 0.4; P , 0.01). During follow-up, increased calcium density and increased mean 18 F-NaF uptake were observed, whereas mean 18 F-FDG uptake decreased. Most noncalcified (86%) and mildly calcified (81%) lesions and 47% of severely calcified lesions had concordant development of both vascular inflammation and osteogenesis. Conclusion: The combination of 18 F-NaF PET imaging and 18 F-FDG PET imaging promotes an understanding of the mechanism of plaque progression, thereby providing new insights into plaque stabilization.

Atherosclerosis imaging with 18F-sodium fluoride PET: state-of-the-art review

“…Eight papers dealt exclusively with the coronary arteries [9][10][11][12][13][14][15][16] and seven solely with the carotid arteries [5,[17][18][19][20][21][22], while only one article focused on the thoracic aorta [23], the infrarenal aorta [24], and the femoral arteries [25]. Four studies were looking on the whole heart and aorta [26][27][28][29], whereas the remaining 11 articles focused also on more than one part of the cardio-arterial system, i.e., coronaries, carotids, and aorta [30][31][32]; coronaries, aorta, and femoral arteries [33]; coronaries and carotids [34]; carotid, aorta, iliac, and femoral arteries [4,35]; carotid, aorta, femoral arteries [36]; carotid, aorta, iliac [37]; carotid, subclavian, iliac, whole aorta [38]; and, finally, aorta and iliac arteries [39].…”

Evolution of arterial [18F]-sodium fluoride uptake and calcification

“…These data validate the finding by Ishiwata et al 14 which reported a strong correlation between [ 18 F]-NaF uptake and calcium volume increase of primarily aortic plaques, over a period of approximatively 1 year. Of note, several other studies reported a similar observation, [15][16][17] while a retrospective study in a population with low incidence of calcification and with a longer follow-up period did not find a similar correlation. 18 Nakahara et al, 12 refined this analysis with the evaluation of the relationship between initial [ 18 F]-NaF uptake and the calcium volume increment over different time intervals.…”

“…22 The association between diffuse calcification and [ 18 F]-NaF uptake remains unclear, with some reports of positive, 11,15 negative 16 or absence of association. 8,10,14,17,18 A portion of this variability between the studies may be explained by the differences in methodology. While not presenting a direct correlation, Nakahara et al 12 showed that the maximal [ 18 F]-NaF uptake during the follow-up correlated with the calcium volume at the end of the study.…”

Imaging Cardiovascular Calcification

“…Li et al119 used 18 F‐NaF and 18 F‐FDG PET/CT to evaluate the association between osteogenesis and inflammation during the progression of calcified plaque. They observed that early atherosclerotic osteogenesis is determined by macrophage accumulation and further intensive progression of arterial calcification might be associated with reduced inflammation.…”