Apoptosis imaging to monitor cancer therapy: the road to fast treatment evaluation?

Molecular imaging of biological processes may allow detection of therapy effects before the tumor is reduced in size. The most frequently used PET tracer in oncology, 2-[18F]fluoro-2-deoxyglucose (FDG), suffers from low specificity due to uptake in inflammatory cells. The proliferation marker, 3'-[18F]fluoro-3'-deoxy-L-thymidine (FLT), is less influenced by the inflammatory response following therapy but here disease- and drug-specific effects need to be considered. Since cancer therapy mainly intends to eliminate cancer cells, imaging of cell death offers a direct way to image therapy response. This review gives an overview of the radiopharmaceutical development and in vivo evaluation of radioligands that have emerged so far for detection and assessment of apoptosis and necrosis. Two radiopharmaceuticals that can image cell death have made it to clinical trials for follow up of tumor treatment: i) 99mTc-and 123I-labelled AnxA5 for the response to treatment of for example lymphoma and lung cancer and ii) 18F-ML10 for the evaluation of brain tumors post-radiation. Other agents need further optimization.