Cutaneous and Vascular Deposits of 18F-NaF by PET/CT in the Follow-Up of Patients with Pseudoxanthoma Elasticum

Abstract

Active microcalcification of elastic fibers is a hallmark of pseudoxanthoma elasticum and it can be measured with the assessment of deposition of 18F-NaF using a PET/CT scan at the skin and vascular levels. It is not known whether this deposition changes over time in absence of specific therapy. We repeated in two years a PET/CT scan using 18F-NaF as a radiopharmaceutical in patients with the disease and compared the deposition at skin and vessel. Furthermore, calcium score values at the vessel wall were also assessed. Main results indicate in the vessel walls that calcification progressed in each patient; by contrast, the active microcalcification, measured and target-to-background ratio showed reduced active deposition. By contrast, at skin levels (neck and axillae) the uptake of the pharmaceutical remains unchanged. In conclusion, because calcification in the arterial wall is not specific for pseudoxanthoma elasticum condition, the measurement of the deposition of 18F-NaF in the neck might be potentially used as a surrogate marker in future trials for the disease.

NaF-PET Imaging of Atherosclerosis Burden

“…Forty-five articles were included in this review [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 ] ( Figure 1 ), to which were added selected articles on methodological and other aspects. Findings in the articles are summarized in the following sections and in Tables S1–S6 in the Supplementary Material .…”

“…NaF uptake and disease progression or ‘prediction’ of events [ 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ];…”

“…Several studies dealt with one arterial bed only, i.e., coronary arteries [ 16 , 17 , 18 , 20 , 29 , 30 , 31 , 38 , 39 , 44 ], global heart [ 22 , 23 , 24 , 25 , 27 , 34 ], pulmonary arteries [ 11 ], left carotid artery [ 28 ], aorta [ 26 , 32 , 41 , 42 , 48 , 49 ], abdominal aorta [ 13 , 33 , 45 ], or several arterial beds [ 5 , 6 , 7 , 8 , 9 , 10 , 12 , 14 , 15 , 21 , 35 , 36 , 37 , 40 , 41 , 43 , 46 , 47 ]. Eight reports were experimental animal studies [ 5 , 6 , 32 , 42 , 43 , 45 , 48 , 49 ], and one was an image case report [ 44 <...…”

“…Lillo et al [ 35 ] found in 14 PXE patients imaged with NaF PET/CT two years apart an overall increase in CT calcification in major extracardial arteries, but this was due to an increase in two patients only; NaF SUVmax and SUVmean remained unchanged, while TBRmax and TBRmean decreased by 24% and 19%, respectively. However, as mentioned, it should be borne in mind that PXE is characterized by primarily medial calcification distinct from conventional atherosclerosis.…”

“…Dissociation between NaF uptake in skin and arteries of PXE patients is also a new observation [ 12 ], as is the aortic/pulmonary dissociation mentioned above between FDG and NaF uptake [ 7 ]. The lack of association between arterial NaF uptake and the Phenodex score [ 12 ] suggests similarities between skin and arterial calcification at the macrocalcification but not microcalcification level, but interpretation is difficult since CT-calcification develops slowly, not only in skin and arteries of PXE patients [ 35 ] but also in angina pectoris patients and healthy controls [ 34 ]. The higher uptake of NaF, but not of FDG, in the abdominal aorta of RA patients and greater average CT calcium volume than in healthy controls [ 13 ] and the higher FDG uptake in carotids and aorta of RA than osteoarthritis patients [ 53 ] are incomparable findings due to diverging quantification measures, i.e., TBRmax vs. blood background corrected SUVmax.…”