Imaging of Therapy-Induced Apoptosis Using 99m Tc-HYNIC-Annexin V in Thymoma Tumor-Bearing Mice

The primary focus of this study was to assess the potential of (99m)Tc-HYNIC-Annexin V for in vivo imaging of apoptosis after systemic chemotherapy and "more localized" radiotherapy in nude mice bearing thymoma tumors and correlating it with TUNEL staining. (99m)Tc-HYNIC-Annexin V was administered intravenously to tumor-bearing mice (n = 25) before and after therapy. Mice were then imaged at 4 hours postinjection, and the animals were subsequently sacrificed. Tumor uptake increased significantly in response to treatment [chemotherapy (n = 8): 1.80 +/- 0.52 %ID/g, p < 0.009; radiotherapy (n = 7): 0.81 +/- 0.07 %ID/g, p < 0.02], compared to the control group (n = 10) (0.57 +/- 0.05 %ID/g). Tumor-to-muscle (T:M) and tumor-to-blood (T:B) ratios were significantly higher in both chemotherapy-treated (p < 0.02 and p < 0.01) and radiotherapy-treated cohorts (p < 0.05 and p < 0.03), compared to the control cohorts at 4 hours postinjection of (99m)Tc-Annxin V. In the post-therapy cohorts, the immunohistochemistry studies indicated a statistically significant correlation between tumor uptake of (99m)Tc-HYNIC-Annexin V and the extent of apoptosis detected by TUNEL-positive staining (r(2) = 0.41). The physiologic localization of the agent was found mainly in the kidneys (34%), liver (11%), and urine (22%). The results suggest that (99m)Tc-HYNIC-Annexin V may be an ideal agent for imaging apoptosis in response to treatment in a thymoma tumor bearing mouse model.