Early decision on
tumor response after anti-
cancer treatment is still an unmet medical need. Here we investigated whether in vivo imaging of apoptosis using linear and cyclic (
disulfide-bonded) form of
ApoPep-1, a
peptide that recognizes
histone H1 exposed on apoptotic cells, at an early stage
after treatment could predict
tumor response to the treatment later. Treatment of stomach
tumor cells with cistplatin or
cetuximab alone induced apoptosis, while combination of
cisplatin plus
cetuximab more efficiently induced apoptosis, as detected by binding with linear and cyclic form of
ApoPep-1. However, the differences between the single agent and combination treatment were more remarkable as detected with the cyclic form compared to the linear form. In
tumor-bearing mice, apoptosis imaging was performed 1 week and 2 weeks after the initiation of treatment, while
tumor volumes and weights were measured 3 weeks after the treatment. In vivo fluorescence imaging signals obtained by the uptake of
ApoPep-1 to
tumor was most remarkable in the group injected with cyclic form of
ApoPep-1 at 1 week after combined treatment with
cisplatin plus
cetuximab. Correlation analysis revealed that imaging signals by cyclic
ApoPep-1 at 1 week
after treatment with
cisplatin plus
cetuximab in combination were most closely related with
tumor volume changes (r2 = 0.934). These results demonstrate that in vivo apoptosis imaging using
Apopep-1, especially cyclic
ApoPep-1, is a sensitive and predictive tool for early decision on stomach
tumor response after anti-
cancer treatment.