Grant: Operating Grant

Apoptosis is a dynamic cellular conversion leading to cell death. It occurs in cancer cells following effective treatment with agents such as chemotherapy and radiotherapy. The presence of apoptosis is therefore an indication of the effectiveness of a particular therapy and could be used to confirm that an effective treatment had been used against human cancer. Apoptosis is readily measured in cultured cells by a variety of techniques but it is very difficult to measure in animals and humans without taking tissue samples. Many attempts have been made to image apoptosis in a living system but to date without much success. This project proposes to develop an imaging agent that will target cells undergoing apoptosis, bind strongly to them and undergo clearance from the rest of the body. Thus the presence of apoptosis could be confirmed soon after a treatment is initiated on a cancer patient using standard medical imaging procedures. The imaging agent we are proposing is based on a type of compound called an aptamer. Aptamers are relatively large molecules composed of nucleic acid units or sometimes of peptide units. To find a binding aptamer we start with a "library" consisting of a huge selection of these nucleic acid compounds and then gradually isolate the few components of the mixture that will bind to cells undergoing apoptosis. Once a binding aptamer is identified it can be stabilized and then labelled with a radioactive tag. Testing of the binding character of the aptamer can be determined in cell cultures and in animal models.