DOTA-DPA {+/-} Zn labeled with 111In or 68Ga for bacterial infection detection

1215 Objectives A dipicolylamine analog ± Zn conjugated with DOTA (DOTA-DPA ± Zn) labeled with 111In and 68Ga is being investigated to selectively target the phosphatidylserine present in bacterial membranes to provide a novel SPECT/PET small molecule to detect bacterial infection and potentially distinguish infection from sterile inflammation. Methods Optimum buffering species, pH, temperature and time were evaluated to identify conditions to provide maximum labeling efficiency and specific activity for both 111In and 68Ga -DOTA-DPA ± Zn. Radiochemical purification and stability were also examined. The 111In-DOTA-DPA ± Zn (0.5-0.8 ug with 20 uCi) was evaluated in mice with S. pyogenes infection in one thigh for biodistribution, clearance and target/normal thigh by biodistribution and SPECT/CT. Results Labeling efficiency of 55-60% was achieved for 111In-labeled DOTA-DPA ± Zn in NH4OAc pH 5.2 at specific activities between 10 and 60 uCi/ug. Similar results were obtained for 68Ga in either HEPES or NH4OAc buffer and ± Zn. Labeling was optimal at 80oC for 20 min. Addition of EDTA showed no change in percent label, and dilution in buffer at RT over 24h showed no instability. Sep-Pak C18 provided 90% plus radiochemical purity with specific activity of ~ 30uCi/ug. Mice with 111In-DOTA-DPA ± Zn at 1h showed the S. pyogenes T/NT ratio of 1.7 and 2.1 for the sample with and without Zn, respectively. About 40-65% of the injected dose remained in animals after 1 h. Also the compound -Zn showed significantly higher accumulation in liver, heart, lungs and blood than with +Zn, although the latter showed higher accumulation in kidneys (10.3%, sd 0.72; vs 5.3%, sd 0.38 inj dose/gram). SPECT at 1h provided T/NT ratios comparable to biodistribution. Conclusions These results show that DOTA-DPA ± Zn can be labeled with either 111In or 68Ga, targets S. pyogenes in mice, and may provide an infection-specific SPECT/PET radiopharmaceutical for eventual use in clinical practice.