Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Radiology, Nuclear Medicine & Medical Imaging, Diagnostic imaging, Apoptosis, Biological therapy, ANNEXIN-V, CELL-DEATH, CHEMOTHERAPY, TC-99M, AGENT, TUMOR, MODEL, PET, A5, PHOSPHATIDYLSERINE, Animals, Annexin A5, Cell Line, Tumor, Fluorine Radioisotopes, Gallium Radioisotopes, Iodine Radioisotopes, Isotope Labeling, Male, Methylmalonic Acid, Mice, Neoplasms, Experimental, Positron-Emission Tomography, Radiopharmaceuticals, Rats, Reproducibility of Results, Sensitivity and Specificity, Treatment Outcome, 1103 Clinical Sciences, Nuclear Medicine & Medical Imaging, 3202 Clinical sciences

Abstract:

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.