Abstract
The noninvasive imaging of cell death, including apoptosis and necrosis, is an important tool for the assessment of degenerative diseases and in the monitoring of tumor treatments. Duramycin is a peptide of 19-amino acids. It binds specifically to phosphatidylethanolamine a novel molecular target for cell death. N-(2-18F-Fluoropropionyl)duramycin ([18F]FPDuramycin) was prepared as a novel positron emission tomography (PET) tracer from the reaction of duramycin with 4-nitrophenyl 2-[18F]fluoropropionate ([18F]NFP). Compared with control cells (viable tumor cells), the in vitro binding of [18F]FPDuramycin with apoptotic cells induced by anti-Fas antibody resulted in a doubling increase, while the binding of [18F]FPDuramycin with necrotic cells induced by three freeze and thaw cycles resulted in a threefold increase. Biodistribution study in mice exhibited its rapid blood and renal clearance and predominant accumulation in liver and spleen over 120 min postinjection. Small-animal PET/CT imaging with [18F]FPDuramycin proved to be a successful way to visualize in vivo therapeutic-induced tumor cell death. In summary, [18F]FPDuramycin seems to be a potential PET probe candidate for noninvasive visualization of in vivo cell death sites induced by chemotherapy in tumors.
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Acknowledgments
We thank Siyuan Gao, Shanzhen He and Kening Wu for technical help and assistance to this study. This work was partly supported by the Tianjin Municipal Science and Technology Commission (No. 11ZCGHHZ00800), National High Technology Research and Development Program of China (863 Program, No. 2008AA02Z430), the National Natural Science Foundation (No. 30970856, No. 81371584, No.81201116), the Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry ([2010]609), Science and Technology Planning Project of Guangzhou (2011J5200025), and the Science Technology Foundation of Guangdong Province (No. 2010B031600054), the Wu jieping Medical Foundation (320675013203).
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The authors declare that they have no conflict of interest.
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Shaobo Yao and Kongzhen Hu contributed equally. Shaobo Yao is currently a PhD Candidate.
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Yao, S., Hu, K., Tang, G. et al. Positron emission tomography imaging of cell death with [18F]FPDuramycin. Apoptosis 19, 841–850 (2014). https://doi.org/10.1007/s10495-013-0964-x
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DOI: https://doi.org/10.1007/s10495-013-0964-x