The imaging of apoptosis with the radiolabeled annexin V: optimal timing for clinical feasibility.

In recent years, the imaging of drug-induced apoptosis has become one of the centers of interest in experimental and clinical research. In particular, the accurate monitoring of chemosensitivity as well as the early prediction of chemoresistance in response to various pro-apoptotic interventions are critical requirements for the best management of oncology patients. The use of technetium [(99m)Tc]-labeled annexin V on animal and human models of cancers provides a proof of principle for the feasibility of a non-invasive, in vivo detection of an apoptotic signal and then for the early assessment of tumor response in the course of chemotherapy. Although promising, however, the initial clinical data point out on the technical limitations that are still to be resolved in terms of tumor-to-background ratio and optimal timing for the imaging of apoptosis. In the present review article, we report the results of animal studies aimed to the evaluation of apoptotic peaks following chemotherapy. In the light of these basic research works, we analyze the profiles of radiolabeled annexin V uptake over time as observed in clinical trials. We then discuss possible new imaging strategies designed to optimize the visualization of apoptotic changes within tumor tissues using the [(99m)Tc]-labeled annexin V. We also suggest longer lived forms of radiolabeled annexin V designed to better understand the temporal patterns of apoptotic tumor response, which in turn, may help to capture the best time-window for the imaging of cell death.