Background and Aims

18F-Fluoride positron emission tomography is a sensitive imaging biomarker that identifies microcalcification in atherosclerotic plaque. Coronary plaques with early microcalcification have an increased propensity to rupture and are associated with acute myocardial infarction.

The study aims to characterise and to define 18F-fluoride uptake in human coronary atherosclerotic plaques.

Methods

Fresh frozen post-mortem human specimens of left coronary artery were imaged using 18F-fluoride micro-positron emission tomography-computed tomography prior to fixation in 10% buffered formalin. Histology, fluorescein-bisphosphonate immunofluorescence and Raman spectroscopy were performed to identify specific regions of hydroxyapatite deposition. Immunohistochemical analysis was undertaken in regions of high 18F-fluoride uptake using markers of tissue mineralisation.

Results

Compared with low levels of non-specific binding in the myocardium, 18F-fluoride demonstrated a high signal to noise ratio in both calcified (median 149.8, interquartile range [IQR] 85.3 to 207.3 kBq/mL) and non-calcified (median 158.1, IQR 121.79 to 234.8 kBq/mL) coronary atherosclerotic plaque. High intensity 18F-fluoride (157 kBq/mL) had a Raman signal at 963 cm^-1corresponding to hydroxyapatite. Areas of enhanced osteopontin and Runt-related transcription factor 2 staining were associated with increased coronary 18F-fluoride uptake (increases of 50.5 [95% confidence interval 28.1 to 72.9] kBq/mL (p<0.0001) and 37.2 [95% confidence interval 12.6 to 61.8] kBq/mL (p=0.0043) respectively).

Conclusions

18F-Fluoride uptake in human coronary atherosclerosis identifies early microcalcification in the form of hydroxyapatite. Coronary plaques with high 18F-fluoride uptake are associated characteristic histologic markers of active mineralisation and atherosclerosis.