Molecular imaging of cell death.

Apoptosis (programmed cell death) and necrosis (uncontrolled cell death) are two distinct processes of cell death that have been described. Non-invasive molecular imaging of these two processes can have several clinical applications and has various approaches in pre-clinical research. Apoptosis imaging enables a specific and early measurement of response in cancer patients. In case of acute myocardial infarction (AMI) and cerebral stroke the degree of both apoptosis and necrosis is abundant. Imaging of both types of cell death is crucial for diagnosis and could differentiate between "real" and "rescuable" cell damage. In a pre-clinical setting cell death imaging offers the possibility for dynamic study protocols and repeated measurements of cell death in the same animal. This review provides an overview of the radiopharmaceutical development and in vivo evaluation of apoptosis and necrosis detecting radioligands that have emerged so far. Some apoptosis radiopharmaceuticals have made it to clinical trials ((99m)Tc-labeled Anx and (18)F-ML-10) while others need further optimization and evaluation (e.g., (18)F-WC-II-89). (99m)Tc-glucarate has been widely used in patients to image necrosis, but this radiopharmaceutical only works early after the onset of necrosis. Other necrosis avid probes like (123)I labeled hypericin and its monocarboxylic acid derivative and (99m)Tc(CO)(3)-bis-hydrazide-bis-DTPA pamoic acid need further evaluation but show already promising results for imaging of necrosis. As a general conclusion molecular imaging of both apoptosis and necrosis is necessary to understand the cell death process in several pathologies.