The in vivo biodistribution of liposomal formulations greatly influences the pharmacokinetics of these novel drugs; therefore the radioisotope labeling of liposomes and the use of nuclear imaging methods for in vivo studies are of great interest. In the present work, a new procedure for the surface labeling of liposomes is presented using the novel 99mTc-tricarbonyl complex. Liposomes mimicking the composition of two FDA approved liposomal drugs were used. In the first step of the labeling, thiol-groups were formed on the surface of the liposomes using Traut’s reagent, which were subsequently used to bind 99mTc-tricarbonyl complex to the liposomal surface. The labeling efficiency determined by size exclusion chromatography was 95%, and the stability of the labeled liposomes in bovine serum was found to be 94% over 2 hours. The obtained specific activity was 50MBq per 1 μmol lipid which falls among the highest values reported for 99mTc labeling of liposomes. Quantitative in vivo SPECT/CT biodistribution studies revealed distinct differences between the labeled liposomes and the free 99mTc-tricarbonyl, which indicates the in vivo stability of the labeling. As the studied liposomes were non-PEGylated, fast clearance from the blood vessels and high uptake in the liver and spleen were observed.
Bibliographical noteFunding Information:
The authors would like to thank Dr. Andreas Vogg for the helpful discussions. This work was jointly supported by the Federal Ministry of Education and Research (BMBF, Germany, Grant no. 01OS14024) and by the National Research, Development and Innovation Office (NKFIH, Hungary, Grant no. TET_12_DE-1-2013-0013). The research leading to these results has received funding from the European Union Seventh Framework Programme FP7/2007-2013 under Grant Agreement no. 305311 (INSERT) and from the Hungarian National Scientific Research Foundation under the ?Development of a Multimodal PET/MRI Imaging Device? (VKSZ_14) research grant. Zoltan Varga and Krisztian Szigetiwere supported by the Janos Bolyai Research Fellowship of the Hungarian Academy of Sciences.
© 2017 Zoltán Varga et al.