Background: Phosphatidylserine (PS)-targeting positron emission tomography (PET) imaging with labeled small-molecule tracer is a crucial non-invasive molecule imaging method of apoptosis. In this study, semi-automatic radiosynthesis and biodistribution of N-(2-F-18-fluoropropionyl)-bis(zinc(II)-dipicolylamine) (F-18-FP-DPAZn2), as a potential small-molecule tracer for PET imaging of cell death in Alzheimer's disease (AD) model, were performed. Methods: F-18-FP-DPAZn2 was synthesized on the modified PET-MF-2V-IT-I synthesizer. Biodistribution was determined in normal mice and PET images of AD model were obtained on a micro PET-CT scanner. Results: With the modified synthesizer, the total decay-corrected radiochemical yield of F-18-FP-DPAZn2 was 35 +/- 6% (n = 5) from F-18(-) within 105 +/- 10 min. Biodistribution results showed that kidney has the highest uptake of F-18-FP-DPAZn2. The uptake of radioactivity in brain kept at a relatively low level during the whole observed time. In vivo F-18-FP-DPAZn2 PET images demonstrated more accumulation of radioactivity in the brain of AD model mice than that in the brain of normal mice. Conclusions: The semi-automatic synthetic method provides a slightly higher radiochemical yield and shorter whole synthesis time of F-18-FP-DPAZn2 than the manual operation method. This improved method can give enough radioactivity and high radiochemical purity of F-18-FP-DPAZn2 for in vivo PET imaging. The results show that F-18-FP-DPAZn2 seems to be a potential cell death tracer for AD imaging.