Bauwens M, De Saint-Hubert M, Cleynhens J, Vandeputte C, Li J, Devos E
Department of Radiopharmacy, KULeuven, Leuven, Belgium.
Q J Nucl Med Mol Imaging. 2013 Jun;57(2):187-200. Epub 2013 Feb 6.
Recently, 18F-labeled 2-(5-fluoropentyl)-2-methylmalonic acid or ML10 has been proposed as a promising PET tracer for imaging of apoptosis. In this study we compared 18F-ML10, the 123I labeled 5-iodo derivative (123I-ML10) and a 68Ga-labeled Annexin A5 (AnxA5) and evaluated them as apoptosis tracers in several distinct models.
In vivo stability and biodistribution were studied in healthy mice. Apoptosis imaging was evaluated in anti-Fas treated mice and mice with muscular apoptosis. Furthermore, 18F-ML10 and 68Ga-Cys2-AnxA5 were evaluated in a rat model with reperfused liver infarct and a rat model with cerebral infarct as well as in Daudi tumor bearing mice, before and after treatment with cyclophosphamide and/or radiotherapy.
18F-ML10 and 68Ga-Cys2-AnxA5 were both stable, while 123I-ML10 metabolized very quickly in vivo. All tracers showed a 3-4 times higher uptake in apoptotic muscular tissue in comparison to that in healthy muscular tissue. Animals with anti-Fas induced hepatic apoptosis showed an increased liver uptake which was most pronounced for 18F-ML10. The uptake of both 18F-ML10 and 68Ga-Cys2-AnxA5 increased in the apoptotic region surrounding the cerebral infarction and the reperfused liver infarction. Tumor uptake of 68Ga-Cys2-AnxA5, but not of 18F-ML10, was statistically significantly higher after therapy as measured with PET/MRI.
All radiotracers were able to detect apoptosis in vitro and in vivo in each of the studied animal models of apoptosis. 68Ga-Cys2-AnxA5, but not 18F-ML10, allowed to visualize the effect of tumor therapy in a statistically significant way.
最近，18F标记的2-(5-氟戊基)-2-甲基丙二酸或ML10已被提议作为一种有前景的用于细胞凋亡成像的正电子发射断层显像（PET）示踪剂。在本研究中，我们比较了18F-ML10、123I标记的5-碘衍生物（123I-ML10）和68Ga标记的膜联蛋白A5（AnxA5），并在几种不同模型中将它们评估为细胞凋亡示踪剂。
在健康小鼠中研究了体内稳定性和生物分布。在抗Fas处理的小鼠和肌肉细胞凋亡的小鼠中评估了细胞凋亡成像。此外，在再灌注肝梗死大鼠模型、脑梗死大鼠模型以及荷Daudi肿瘤小鼠中，在环磷酰胺和/或放疗治疗前后，对18F-ML10和68Ga-Cys2-AnxA5进行了评估。
18F-ML10和68Ga-Cys2-AnxA5均稳定，而123I-ML10在体内代谢非常快。与健康肌肉组织相比，所有示踪剂在凋亡肌肉组织中的摄取均高出3 - 4倍。抗Fas诱导肝细胞凋亡的动物肝脏摄取增加，这在18F-ML10中最为明显。在脑梗死和再灌注肝梗死周围的凋亡区域，18F-ML10和68Ga-Cys2-AnxA5的摄取均增加。用PET/MRI测量，治疗后68Ga-Cys2-AnxA5的肿瘤摄取在统计学上显著高于18F-ML10。
所有放射性示踪剂均能够在体外和体内在所研究的每种细胞凋亡动物模型中检测到细胞凋亡。68Ga-Cys2-AnxA5能够以统计学上显著的方式显示肿瘤治疗效果，而18F-ML10则不能。
