68Ga-DOTA-Puromycin: In vivo imaging of bacterial infection
2013
1218 Objectives We recently proofed the suitability of 68Ga-DOTA-Puromycin to image increased protein synthesis in mycoplasmic infections in rabbits. Therefore, the purpose of this study was to evaluate the potential of 68Ga-DOTA-Puromycin for the use as imaging agent of bacterial infection by determining protein synthesis of bacterial colonies in contrast to unspecific inflammation. Methods DOTA-Pur was purchased from Purimex, Germany and desalted and purified on Strata-X columns. A TiO2-based 68Ge/68Ga generator was eluted fractionally to obtain 68Ga in 2 ml 0.6 M HCL. After pH-adjustment, DOTA-Puromycin was added, incubated 20 min at 95° C and purified on Strata-X columns. Quality control was performed on TLC. Purity was determined by RP-HPLC. In vivo biodistribution of 68Ga-DOTA-Puromycin was studied by µPET/CT imaging on mice carrying non-bacterial inflammation (turpentine oil) and infections with Staphylococcus Aureus. Results Optimal labeling conditions, i.e. compound and buffer molarity, pH, temperature and incubation time were evaluated resulting in high labeling efficiency of 65 ± 2.6 % and RCP of ≥ 98%. Preliminary ex vivo results showed blood clearance within 60 min p.i. via-renal excretion. At 60 min p.i. no activity was found in potential target organs for infection, i.e. lung, brain, musculoskeletal system or abdomen. No in vivo accumulation of 68Ga-DOTA-Puromycin in unspecific inflammations could be detected, whereas accumulation of 68Ga-DOTA-Puromycin in subcutaneous colonies of S. Aureus resulted in high contrst µPET/CT images showing clear outlines of the infections. Conclusions Successful radiolabeling and in vivo biodistribution of 68Ga-DOTA-Puromycin revealed very promising properties for an infection imaging agent. Research Support This work has been supported by fundings from the NPI AS CR.
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