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?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.