Hot Article: A better view of cell death
23 February 2009
A new class of radio-labelled compounds that can image dying cells could be used to show if drugs are effective at blocking or inducing cell death, say US scientists.
Apoptosis, or programmed cell death, is one of the ways the body removes cells that no longer function properly. An abnormal increase in apoptosis can lead to conditions such as neurodegeneration and stroke. On the other hand, cancer cells are protected against apoptosis and so patients are often resistant to chemotherapy that is meant to kill the cancer cells. Scientists are interested in drugs that either block or induce apoptosis to treat these conditions.

A micro positron emission tomography image of mouse treated with radiotracer. GB indicates the gall bladder. |
Robert Mach and colleagues at Washington University School of Medicine, St Louis, made radio-labelled inhibitors of caspase-3, an enzyme that plays a vital role in apoposis. They injected the compounds into mice that had increased levels of liver apoptosis. They showed that the radio-labelled compounds inhibited caspase-3 and were retained in the liver. Mach says the results suggest that the compounds are potential radiotracers for imaging cell death and could be used to demonstrate whether a drug is effective at blocking or inducing apoptosis.
'Apoptosis is not the only mechanism by which cells die,' says Mach. He aims to develop radiotracers that can be used to measure the other pathways of cell death, necrosis (caused by external factors such as infection) and autophagy (a type of programmed cell death where a cell's own enzymes degrade its components). 'A non-invasive imaging procedure that can independently measure the different pathways of cell death will provide a valuable research tool for determining the physiological conditions favouring one form of cell death versus the others,' he adds.
Joanne Thomson
Link to journal article
[18F]- and [11C]-Labeled N-benzyl-isatin sulfonamide analogues as PET tracers for Apoptosis: synthesis, radiolabeling mechanism, and in vivo imaging study of apoptosis in Fas-treated mice using [11C]WC-98
Dong Zhou, Wenhua Chu, Delphine L. Chen, Qi Wang, David E. Reichert, Justin Rothfuss, Andre D'Avignon, Michael J. Welch and Robert H. Mach, Org. Biomol. Chem., 2009, 7, 1337
DOI: 10.1039/b819024k
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