In vivo imaging of apoptosis in a preclinical setting in anticancer
drug development could provide remarkable advantages in terms of translational medicine. So far, several imaging technologies with different probes have been used to achieve this goal. Here we describe a bioluminescence imaging approach that uses a new formulation of
Z-DEVD-aminoluciferin, a
caspase 3/7 substrate, to monitor in vivo apoptosis in
tumor cells engineered to express
luciferase. Upon apoptosis induction,
Z-DEVD-aminoluciferin is cleaved by
caspase 3/7 releasing aminoluciferin that is now free to react with
luciferase generating measurable light. Thus, the activation of
caspase 3/7 can be measured by quantifying the bioluminescent signal. Using this approach, we have been able to monitor
caspase-3 activation and subsequent apoptosis induction after
camptothecin and
temozolomide treatment on xenograft mouse models of
colon cancer and
glioblastoma, respectively. Treated mice showed more than 2-fold induction of
Z-DEVD-aminoluciferin luminescent signal when compared to the untreated group. Combining
D: -luciferin that measures the total
tumor burden, with
Z-DEVD-aminoluciferin that assesses apoptosis induction via
caspase activation, we confirmed that it is possible to follow non-invasively
tumor growth inhibition and induction of apoptosis
after treatment in the same animal over time. Moreover, here we have proved that following early apoptosis induction by
caspase 3 activation is a good
biomarker that accurately predicts
tumor growth inhibition by anti-
cancer drugs in engineered
colon cancer and
glioblastoma cell lines and in their respective mouse xenograft models.