Hyafil Fabien, Tran-Dinh Alexy, Burg Samuel, Leygnac Sébastien, Louedec Liliane, Milliner Milan, Ben Azzouna Rana, Reshef Ayelet, Ben Ami Miri, Meilhac Olivier, Le Guludec Dominique
Mol Imaging. 2015;14:433-42.
[18F]ML-10 (2-(5-fluoro-pentyl)-2-methylmalonic acid) is a positron emission tomography (PET) radiotracer that accumulates in cells presenting apoptosis-specific membrane alterations. The aim of this study was to test whether [18F]ML-10 allows for the detection of apoptotic cells located in atherosclerotic plaques in rabbits. Atherosclerotic plaques were induced in the aortas of five rabbits, and five additional rabbits were used as controls. Activity in the aortas was quantified in vivo and ex vivo. The localization of [18F]ML-10 to the aortic wall was identified by autoradiography. Average target to background ratios measured in vivo by PET were higher in the aortas of atherosclerotic rabbits compared with those of control rabbits (2.00 ± 0.52 vs 1.22 ± 0.30; p < .05). Differences in [18F]ML-10 uptake between atherosclerotic and control aortas were confirmed ex vivo by PET and gamma counting (23.9 ± 11.2 vs 1.1 ± 2.4 counts/pixel; p <.05; 3.6 ± 2.0 vs 0.05 ± 0.05 % of injected activity/g; p < .05, respectively). Strong correlation was observed between the accumulation of [18F]ML-10 in aortic segments as detected by autoradiography and the number of apoptotic cells on corresponding histologic sections (r2 = .75; p < .05). In this study, we found that atherosclerotic plaques rich in apoptotic cells can be detected with [18F]ML-10 and PET.
[18F]ML-10(2-(5-氟戊基)-2-甲基丙二酸)是一种正电子发射断层扫描(PET)放射性示踪剂,可在呈现凋亡特异性膜改变的细胞中蓄积。本研究的目的是测试[18F]ML-10是否能够检测兔动脉粥样硬化斑块中的凋亡细胞。在5只兔的主动脉中诱导形成动脉粥样硬化斑块,另外5只兔用作对照。对主动脉中的活性进行体内和体外定量。通过放射自显影确定[18F]ML-10在主动脉壁的定位。与对照兔相比,PET在体内测量的动脉粥样硬化兔主动脉的平均靶本底比值更高(2.00±0.52对1.22±0.30;p<.05)。PET和γ计数在体外证实了动脉粥样硬化和对照主动脉之间[18F]ML-10摄取的差异(23.9±11.2对1.1±2.4计数/像素;p<.05;分别为注射活性/g的3.6±2.0对0.05±0.05%;p<.05)。放射自显影检测到的主动脉节段中[18F]ML-10的蓄积与相应组织学切片上的凋亡细胞数量之间观察到强相关性(r2=.75;p<.05)。在本研究中,我们发现富含凋亡细胞的动脉粥样硬化斑块可用[18F]ML-10和PET检测到。