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

Autor: Bauwens, M., De Saint-Hubert, M., Cleynhens, J., Vandeputte, C., Li, J., Devos, E., Hendrickx, S., Ni, Y., Reutelingsperger, C.P., Mortelmans, L., Mottaghy, F.M., Verbruggen, A.
Přispěvatelé: MUMC+: DA BV Medische staf (6), Biochemie, RS: NUTRIM - R1 - Metabolic Syndrome, Genetica & Celbiologie, RS: CARIM School for Cardiovascular Diseases
Jazyk: angličtina
Rok vydání: 2013
Zdroj: Quarterly Journal of Nuclear Medicine and Molecular Imaging, 57(2), 187-200. Edizioni Minerva Medica S.p.A.
ISSN: 1824-4785
Popis: 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.
Databáze: OpenAIRE