Choong Mo Kang1, Hyun-Jung Koo, Sangbin Lee, Kyo Chul Lee, Yu-Kyoung Oh, Yearn Seong Choe. 1. Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-ku, Seoul 135-710, South Korea; Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 135-710, South Korea.
Abstract
INTRODUCTION: We synthesized and evaluated (64)Cu-labeled tetraiodothyroacetic acid (tetrac)-conjugated liposomes for PET imaging of tumor angiogenesis, because tetrac inhibits angiogenesis via integrin αVβ3. METHODS: Tetrac-PEG-DSPE and DOTA-PEG-DSPE were synthesized and formulated with other lipids into liposomes. The resulting tetrac/DOTA-liposomes were labeled with (64)Cu at 40 °C for 1 h and purified using a PD-10 column. (64)Cu-DOTA-liposomes were also prepared for comparison. Human aortic endothelial cell (HAEC) binding studies were performed by incubating the liposomes with the cells at 37 °C. MicroPET imaging followed by tissue distribution study was carried out using U87MG tumor-bearing mice injected with tetrac/(64)Cu-DOTA-liposomes or (64)Cu-DOTA-liposomes. RESULTS: HAEC binding studies exhibited that tetrac/(64)Cu-DOTA-liposomes were avidly taken up by the cells from 1.02 %ID at 1 h to 11.89 %ID at 24 h, while (64)Cu-DOTA-liposomes had low uptake from 0.47 %ID at 1 h to 1.57 %ID at 24 h. MicroPET imaging of mice injected with tetrac/(64)Cu-DOTA-liposomes showed high radioactivity accumulation in the liver and spleen. ROI analysis of the tumor images revealed 1.93 ± 0.12 %ID/g at 1 h and 2.70 ± 0.36 %ID/g at 22 h. In contrast, tumor ROI analysis of (64)Cu-DOTA-liposomes revealed 0.54 ± 0.08 %ID/g at 1 h and 0.52 ± 0.09 %ID/g at 22 h. Tissue distribution studies confirmed that the tumor uptakes of tetrac/(64)Cu-DOTA-liposomes and (64)Cu-DOTA-liposomes were 1.75 ± 0.03 %ID/g and 0.36 ± 0.01 %ID/g at 22 h, respectively. CONCLUSION: These results demonstrate that tetrac/(64)Cu-DOTA-liposomes have significantly enhanced tumor uptake compared to (64)Cu-DOTA-liposomes due to tetrac conjugation. Further studies are warranted to reduce the liver and spleen uptake of tetrac/(64)Cu-DOTA-liposomes.
INTRODUCTION: We synthesized and evaluated (64)Cu-labeled tetraiodothyroacetic acid (tetrac)-conjugated liposomes for PET imaging of tumor angiogenesis, because tetrac inhibits angiogenesis via integrin αVβ3. METHODS:Tetrac-PEG-DSPE and DOTA-PEG-DSPE were synthesized and formulated with other lipids into liposomes. The resulting tetrac/DOTA-liposomes were labeled with (64)Cu at 40 °C for 1 h and purified using a PD-10 column. (64)Cu-DOTA-liposomes were also prepared for comparison. Human aortic endothelial cell (HAEC) binding studies were performed by incubating the liposomes with the cells at 37 °C. MicroPET imaging followed by tissue distribution study was carried out using U87MG tumor-bearing mice injected with tetrac/(64)Cu-DOTA-liposomes or (64)Cu-DOTA-liposomes. RESULTS:HAEC binding studies exhibited that tetrac/(64)Cu-DOTA-liposomes were avidly taken up by the cells from 1.02 %ID at 1 h to 11.89 %ID at 24 h, while (64)Cu-DOTA-liposomes had low uptake from 0.47 %ID at 1 h to 1.57 %ID at 24 h. MicroPET imaging of mice injected with tetrac/(64)Cu-DOTA-liposomes showed high radioactivity accumulation in the liver and spleen. ROI analysis of the tumor images revealed 1.93 ± 0.12 %ID/g at 1 h and 2.70 ± 0.36 %ID/g at 22 h. In contrast, tumor ROI analysis of (64)Cu-DOTA-liposomes revealed 0.54 ± 0.08 %ID/g at 1 h and 0.52 ± 0.09 %ID/g at 22 h. Tissue distribution studies confirmed that the tumor uptakes of tetrac/(64)Cu-DOTA-liposomes and (64)Cu-DOTA-liposomes were 1.75 ± 0.03 %ID/g and 0.36 ± 0.01 %ID/g at 22 h, respectively. CONCLUSION: These results demonstrate that tetrac/(64)Cu-DOTA-liposomes have significantly enhanced tumor uptake compared to (64)Cu-DOTA-liposomes due to tetrac conjugation. Further studies are warranted to reduce the liver and spleen uptake of tetrac/(64)Cu-DOTA-liposomes.
Authors: Scott Edmonds; Alessia Volpe; Hilary Shmeeda; Ana C Parente-Pereira; Riya Radia; Julia Baguña-Torres; Istvan Szanda; Gregory W Severin; Lefteris Livieratos; Philip J Blower; John Maher; Gilbert O Fruhwirth; Alberto Gabizon; Rafael T M de Rosales Journal: ACS Nano Date: 2016-10-26 Impact factor: 15.881