Objective: 18 F-sodium fluoride ( 18 F-NaF) positron emission tomography (PET) imaging is thought to visualize active atherosclerotic plaque calcification. This is supported by the binding of 18 F-NaF to plaque calcification ex vivo, but no prior studies have examined binding of 18 F-NaF to human-like plaque in vivo. Our aim was to validate the specificity of 18 F-NaF PET for plaque calcifications in atherosclerotic minipigs. Approach and Results: Gain-of-function PCSK9 D374Y (proprotein convertase/subtilisin kexin type 9) transgenic Yucatan minipigs (n=4) were fed high-fat diet for 2.5 years to develop atherosclerosis and then subjected to 18 F-NaF PET/computed tomography imaging. The heart, aorta, and iliac arteries were immediately re-scanned ex vivo after surgical extraction. Lesions from the abdominal aorta, iliac arteries, and coronary arteries were cryo-sectioned for autoradiography. Histological plaque characteristics, PET/computed tomography signal, and autoradiography were linked through regression and co-localization analysis. Arterial 18 F-NaF PET signal had intensities comparable to clinical scans and colocalized moderately with calcification detected by computed tomography. Histological analysis showed calcification spanning from microcalcifications near lipid pools and necrotic core to more homogenous macrocalcifications. Comparison with arteries from autopsy cases confirmed the resemblance in localization and appearance with early human plaque calcification. Regression analysis in the abdominal aorta showed correlations with calcified plaque but could not rule out contributions from noncalcified plaque. This was resolved by autoradiography, which showed specific accumulation in plaque calcifications in all examined arteries. In the context of porcine abdominal aorta, 18 F-NaF PET imaging was, however, less accurate than computed tomography for detecting small calcifications. Conclusions: 18 F-NaF accumulates specifically in calcifications of atherosclerotic plaques in vivo.

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BackgroundIn vivo determination of regional pulmonary blood flow (PBF) is a valuable tool for the evaluation of many lung diseases. In this study, the use of 68Ga-DOTA PET for the in vivo quantitative determination of regional PBF is proposed. This methodology was implemented and tested in healthy pigs and validated using fluorescent microspheres. The study was performed on young large white pigs (n = 4). To assess the reproducibility and consistency of the method, three PET scans were obtained for each animal. Each radiotracer injection was performed simultaneously to the injection of fluorescent microspheres. PBF images were generated applying a two-compartment exchange model over the dynamic PET images. PET and microspheres values were compared by regression analysis and Bland–Altman plot.ResultsThe capability of the proposed technique to produce 3D regional PBF images was demonstrated. The correlation evaluation between 68Ga-DOTA PET and microspheres showed a good and significant correlation (r = 0.74, P < 0.001).ConclusionsAssessment of PBF with the proposed technique allows combining the high quantitative accuracy of PET imaging with the use of 68Ga/68Ge generators. Thus, 68Ga-DOTA PET emerges as a potential inexpensive method for measuring PBF in clinical settings with an extended use.Electronic supplementary materialThe online version of this article (doi:10.1186/s13550-017-0259-2) contains supplementary material, which is available to authorized users.