Merve KARPUZ, Emre OZGENC, Evren ATLIHAN GUNDOGDU, Zeynep BURAK

Pre-Study on Radiolabeling of Colistin with Lutetium-177 to Develop Theranostic Infection Agent

Infection is one of the important burdens on the health care system, not only due to leading morbidity and mortality but also because of the development of antibiotic resistance. Although the infection can be diagnosed by imaging techniques, more effective agents including radiopharmaceuticals may be required to image deep-seated infections. Imaging also plays a critical role in the choosing of optimum treatment options and following treatment. Theranostic agents offer many advantages such as monitoring the biodistribution and targeting of therapeutic agents, as well as rapid diagnosis and treatment. Colistin, a cationic peptide, leads to bacterial death through interaction with lipopolysaccharides in the cell wall of bacteria. In our study, 177Lu as radionuclide part and colistimethate sodium (a prodrug of colistin, CMS) as pharmaceutic part were chosen to prepare a radiopharmaceutical for imaging and treatment of infections. 177Lu-CMS complex was formed under room condition, and radiolabeling efficiency was determined by paper and high-performance liquid chromatography. The effect of the filtration process on radiolabeling was evaluated among the labeling efficiencies of filtered and un-filtered complexes. The different incubation times (5, 30, and 60 min) effect on the radiolabeling process was also evaluated. Moreover, in vitro stability of 177Lu-CMS complex in saline solution was assessed during 7 days. According to the results, desired radiolabeling efficiency was not obtained under tested conditions and stability studies. Therefore, various modifications such as the addition of chelating agents or stabilizers in the radiolabeling procedure should be made to increase the radiolabeling stability. Further studies regarding radiolabeling are surely needed, and our studies are continuing.

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