Extended-release PEG-luciferin allows for long-term imaging of firefly luciferase activity in vivo.
Bioluminescence has gained favour in the last decade as an approach for observing tumours in vivo in a non-destructive manner. This very sensitive technique is based on light emission by the reaction of luciferin with the enzyme luciferase, as measured by a photodetector. Ever since the development of recombinant tumour cell lines that have been engineered to produce luciferase, a vast number of experiments have been carried out examining tumour growth, tumour metastasis and the effect of therapeutic regimens in such cases. A primary stumbling block, however, is the relatively short circulatory half-life of luciferin. In this paper, we propose the PEGylation of 6-amino-D-luciferin to extend its in vivo circulatory half-life, thus making the possibility of long-term observations in animals possible. The covalent attachment was through a carbamate linker that is known to hydrolyse in vivo, releasing the parent compound. Based on our studies, longer emission of the PEGylated luciferin was observed, as compared to free luciferin in mice bearing PC3 prostate tumours expressing luciferase. This result suggests that this reagent can be used in applications requiring extended monitoring of luciferase activation in vivo.
Chandran
Sachin S
SS
Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21231, USA.
Williams
Simon A
SA
Denmeade
Samuel R
SR
D000818:Animals; D045744:Cell Line, Tumor; D048888:Fireflies / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D015394:Molecular Structure; D009368:Neoplasm Transplantation; D011092:Polyethylene Glycols / Q000737:chemistry*; D013844:Thiazoles / Q000032:analysis* / Q000737:chemistry* / Q000378:metabolism
D013844:Thiazoles; D011092:Polyethylene Glycols; D008156:Luciferases