F-18 Sodium fluoride positron emission tomography for myocardial infarction imaging

Objectives F-18 sodium fluoride (Na18F) is a well-known PET agent avid for calcification. Tissue injury such as myocardial infarction (MI) may be visualized using Na18F PET. We aimed to investigate Na18F PET findings in rat MI models and to correlate the findings with apoptosis and calcification.

Methods Female Spraque-Dawley rats (270-510g) were used for the MI experiments. MI was induced by ligation of coronary artery during open thoracotomy under ventilator control and confirmed by TTC staining. Na18F (dose; 11.1-18.5 MBq) was injected intravenously and PET images were taken 30 minutes later using an animal dedicated PET scanner (NanoPET/CT, Mediso). Uptake of Na18F in MI was quantitated using the standardized uptake value (SUV). Lung was used as a control for SUV normalization. Apoptosis-targeted peptide labeled with red fluorescent dye (excitation/emission wavelength, 554/584 nm; AHR553; Bioacts) was injected to the rat 2 hrs before sacrifice and harvested heart slices (2-mm thick) were imaged using IVIS imaging system (Lumina-II, PerkinElmer). Then heart slices were paraffin-embedded and sliced into 5-μm thick sections. TUNEL staining for apoptosis and von Kossa’s staining for calcification were performed finally.

Results Na18F uptake in MI started to increase from 3hrs (SUV ratio of MI/lung in mean±SEM, 1.32±0.19, n=3), reached maximum at day1 (4.56±0.74, n=7), maintained plateau until day3 (4.03±0.54, n=3) and then almost disappeared at day8 (1.48±0.20, n=2) post MI (p=0.023, Kruskal-Wallis test). Na18F uptake in MI was matched with apoptotic area as revealed on apoptosis-targeted peptide uptake and TUNEL staining (Figure) at day 1 post MI. However, calcium staining by Von Kossa’s method did not show compatible uptake at the MI area.

Conclusions Na18F uptake in MI could be visualized using PET in rat MI model in vivo. The pattern of Na18F uptake reached maximum at day1 and disappeared at day8 post MI. Apoptotic change in MI tissue may be attributed to Na18F uptake at the time when calcium uptake would not take place.