Molecular Imaging of Apoptosis for Early Prediction of Therapy Efficiency
Marijke De Saint-Hubert, Matthias Bauwens and Felix M. Mottaghy
Affiliation: Nuclear Medicine, MUMC+, Maastricht, The Netherlands ; P.O. Box 5800, 6202 AZ Maastricht.
Keywords: Molecular imaging, apoptosis, early cancer therapy evaluation.
Evasion of apoptosis is one of the hallmarks of cancer and any effective therapy primarily attempts to induce apoptosis. The
evaluation of the degree of success of cancer therapy is currently mainly based on clinical and laboratory parameters and in a later stage
on tumor shrinkage. However, none of these parameters provide an objective and early analysis of a therapeutic effect. Molecular imaging
may provide a tool for this purpose by using not only pathophysiological but also biochemical effects of the therapy. First in the field,
FDG-PET has been explored and demonstrated to offer insight in the amount of viable cells, even though false positives are commonly
due to the lack of specificity of this particular radiopharmaceutical. More specific markers target the dying cells instead of those remaining
alive. Specific apoptosis markers have been developed of which the radiolabeled Annexin A5 is the most intensely studied probe.
Site-specific labeling strategies have improved this imaging probe with good results both in pre-clinical studies and in clinical trials, with
promises for clinical applications. Caspase sensitive probes, such as the isatines, can also effectively image apoptosis but are limited due
to the high background activities. More recent discoveries of small apoptosis sensitive probes, such as 18F-ML10, are currently being explored.
In this review, the most important apoptosis sensitive probes are described from both a pre-clinical and a clinical perspective,
highlighting their potential but also their limitations as an early marker for therapeutic success. It seems that apoptosis imaging can help
to guide therapy, not by replacing the current methodology but by providing additional and useful information.
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