A cyclic HSV1-TK reporter for real-time PET imaging of apoptosis.
The coordination of cell proliferation and programmed death (apoptosis) is essential for normal physiology, and imbalance in these two opposing processes is implicated in various diseases. Objective and quantitative noninvasive imaging of apoptosis would significantly facilitate rapid screening as well as validation of therapeutic chemicals. Herein, we molecularly engineered an apoptosis switch-on PET-based cyclic herpes simplex virus type 1-thymidine kinase reporter (cTK266) containing a caspase-3 recognition domain as the switch. Translation of the reporter and protein splicing in healthy mammalian cells produce an inactive cyclic chimera. Upon apoptosis, caspase-3-specific cleavage of the circular product occurs, resulting in the restoration of the thymidine kinase activity, which can be detected in living cells and animals by noninvasive PET imaging. Our results showed the high sensitivity of this reporter in dynamic and quantitative imaging of apoptosis in living subjects. This reporter could be applied as a valuable tool for high-throughput functional screening of proapoptotic and antiapoptotic compounds in preclinical models in drug development, and monitoring the destination of therapeutic cells in clinical settings.
School of Life Science and Technology, Xidian University, Xi'an, Shaanxi 710071, China.
Fu
F
Wang
Zhe
Z
Wang
Naoki
N
Hida
Dale O
DO
Kiesewetter
Ying
Y
Ma
Kai
K
Yang
Pengfei
P
Rong
Jimin
J
Liang
Jie
J
Tian
Gang
G
Niu
Xiaoyuan
X
Chen
D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D005260:Female; D017930:Genes, Reporter; D018259:Herpesvirus 1, Human / Q000201:enzymology*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D049268:Positron-Emission Tomography; D013937:Thymidine Kinase / Q000235:genetics*
D013937:Thymidine Kinase
positron-emission tomography; reporter probe