Longitudinal PET Imaging of Doxorubicin-Induced Cell Death with 18F-Annexin V

Purpose: This study aims to apply longitudinal positron emission tomography (PET) imaging with (18) F-Annexin V to visualize and evaluate cell death induced by doxorubicin in a human head and neck squamous cell cancer UM-SCC-22B tumor xenograft model. Procedures: In vitro toxicity of doxorubicin to UM-SCC-22B cells was determined by a colorimetric assay. Recombinant human Annexin V protein was expressed and purified. The protein was labeled with fluorescein isothiocyanate for fluorescence staining and (18) F for PET imaging. Established UM-SCC-22B tumors in nude mice were treated with two doses of doxorubicin (10 mg/kg each dose) with 1 day interval. Longitudinal (18) F-Annexin V PET was performed at 6 h, 24 h, 3 days, and 7 days after the treatment started. Following PET imaging, direct tissue biodistribution study was performed to confirm the accuracy of PET quantification. Results: Two doses of doxorubicin effectively inhibited the growth of UM-SCC-22B tumors by inducing cell death including apoptosis. The cell death was clearly visualized by (18) F-Annexin V PET. The peak tumor uptake, which was observed at day 3 after treatment started, was significantly higher than that in the untreated tumors (1.56 +/- 0.23 vs. 0.89 +/- 0.31%ID/g, p < 0.05). Moreover, the tumor uptake could be blocked by co-injection of excess amount of unlabeled Annexin V protein. At day 7 after treatment, the tumor uptake of (18) F-Annexin had returned to baseline level. Conclusions: (18) F-Annexin V PET imaging is sensitive enough to allow visualization of doxorubicin-induced cell death in UM-SCC-22B xenograft model. The longitudinal imaging with (18) F-Annexin will be helpful to monitor early response to chemotherapeutic anti-cancer drugs.