Evaluation of [64Cu]DOTA-annexin V radiotracer in the cycloheximide-induced liver apoptosis model

Objectives This study was designed to evaluate [⁶⁴Cu] labeled annexin V as a PET tracer in a rat model of cycloheximide (CHX) induced liver apoptosis.

Methods A pilot study showed that a single IV injection of CHX rapidly induced liver apoptosis in rat dose-dependently; maximum apoptosis in the liver occurred at 3 h after CHX treatment. In this study, male Sprague Dawley (SD) rats were treated IV with 5 or 10mg/kg CHX to induce liver apoptosis. 3 h after the treatment, rats were imaged for 90min with 0.5-1.0 µCi/g [⁶⁴Cu] labeled annexin V. The livers were harvested at the end of the scan for ex vivo autoradiography and terminal deoxynucleotide end-labeling (TUNEL) staining.

Results Annexin V tracer uptake in the liver increased dose dependently with CHX treatment. Liver uptake ratios (treated/control) were 2.87 and 3.39 for 5 and 10 mg/kg respectively. Kidney uptake decreased with increased CHX dose. There were no differences in the blood pool activity between treated and control rats. Ex vivo autoradiography and TUNEL staining showed good correlation of annexin V uptake with TUNEL-positive cells. There was a positive correlation between liver annexin V standardized uptake values at the end of the PET scan and numbers of the TUNEL-positive cells.

Conclusions PET studies combined with ex vivo autoradiography and TUNEL staining showed that uptake of [⁶⁴Cu] labeled annexin V correlates well with the level of apoptotic cells in this CHX induced liver apoptosis model.