Matter Christian M, Wyss Matthias T, Meier Patricia, Späth Nicolas, von Lukowicz Tobias, Lohmann Christine, Weber Bruno, Ramirez de Molina Ana, Lacal Juan Carlos, Ametamey Simon M, von Schulthess Gustav K, Lüscher Thomas F, Kaufmann Philipp A, Buck Alfred
Cardiovascular Research, Institute of Physiology, University of Zurich, Cardiovascular Center, Switzerland.
Arterioscler Thromb Vasc Biol. 2006 Mar;26(3):584-9. doi: 10.1161/01.ATV.0000200106.34016.18. Epub 2005 Dec 15.
Current imaging modalities of atherosclerosis mainly visualize plaque morphology. Valuable insight into plaque biology was achieved by visualizing enhanced metabolism in plaque-derived macrophages using 18F-fluorodeoxyglucose (18F-FDG). Similarly, enhanced uptake of 18F-fluorocholine (18F-FCH) was associated with macrophages surrounding an abscess. As macrophages are important determinants of plaque vulnerability, we tested 18F-FCH for plaque imaging.
We injected 18F-FCH (n=5) or 18F-FDG (n=5) intravenously into atherosclerotic apolipoprotein E-deficient mice. En face measurements of aortae isolated 20 minutes after 18F-FCH injections demonstrated an excellent correlation between fat stainings and autoradiographies (r=0.842, P<0.0001), achieving a sensitivity of 84% to detect plaques by 18F-FCH. In contrast, radiotracer uptake 20 minutes after 18F-FDG injections correlated less with en face fat stainings (r=0.261, P<0.05), reaching a sensitivity of 64%. Histological analyses of cross-sections 20 minutes after coinjections of 18F-FCH and 14C-FDG (n=3) showed that 18F-FCH uptake correlated better with fat staining (r=0.740, P<0.0001) and macrophage-positive areas (r=0.740, P<0.0001) than 14C-FDG (fat: r=0.236, P=0.29 and CD68 staining: r=0.352, P=0.11), respectively.
18F-FCH identifies murine plaques better than 18F-FDG using ex vivo imaging. Enhanced 18F-FCH uptake into macrophages may render this tracer a promising candidate for imaging plaques in patients.
目前动脉粥样硬化的成像方式主要用于观察斑块形态。通过使用18F-氟脱氧葡萄糖(18F-FDG)观察斑块衍生巨噬细胞中增强的代谢,对斑块生物学有了宝贵的认识。同样,18F-氟胆碱(18F-FCH)摄取增强与脓肿周围的巨噬细胞有关。由于巨噬细胞是斑块易损性的重要决定因素,我们测试了18F-FCH用于斑块成像。
我们将18F-FCH(n = 5)或18F-FDG(n = 5)静脉注射到动脉粥样硬化载脂蛋白E缺陷小鼠体内。在注射18F-FCH后20分钟分离主动脉进行表面测量,结果显示脂肪染色与放射自显影之间具有良好的相关性(r = 0.842,P < 0.0001),18F-FCH检测斑块的灵敏度达到84%。相比之下,注射18F-FDG后20分钟的放射性示踪剂摄取与表面脂肪染色的相关性较小(r = 0.261,P < 0.05),灵敏度为64%。对同时注射18F-FCH和14C-FDG(n = 3)后20分钟的横截面进行组织学分析表明,18F-FCH摄取与脂肪染色(r = 0.740,P < 0.0001)和巨噬细胞阳性区域(r = 0.740,P < 0.0001)的相关性分别优于14C-FDG(脂肪:r = 0.236,P = 0.29;CD68染色:r = 0.352,P = 0.11)。
使用离体成像,18F-FCH比18F-FDG能更好地识别小鼠斑块。巨噬细胞对18F-FCH摄取增强可能使这种示踪剂成为患者斑块成像的有希望的候选者。