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The Quarterly Journal of Nuclear Medicine and Molecular Imaging 2013 June;57(2):187-200


language: English

In vitro and in vivo comparison of 18F and 123I-labeled ML10 with 68Ga-Cys2-AnxA5 for molecular imaging of apoptosis

Bauwens M. 1, 6, De Saint-Hubert M. 2, 6, Cleynhens J. 1, Vandeputte C. 2, Li J. 3, Devos E. 4, Hendrickx S. 1, Ni Y. 3, Reutelingsperger C. 4, Mortelmans L. 2, Mottaghy F. M. 2, 5, 6, Verbruggen A. 1

1 Department of Radiopharmacy, KULeuven, Leuven, Belgium; 2 Department of Nuclear Medicine, KULeuven, Leuven, Belgium; 3 Department of Radiology, KULeuven, Leuven, Belgium; 4 Department of Biochemistry, Maastricht University, The Netherlands; 5 Department of Nuclear Medicin, RWTH Aachen, Germany; 6 Department of Nuclear Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands


Aim: 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.
Methods: 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.
Results: 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.
Conclusion: 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.

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