64Cu-Labeled tetraiodothyroacetic acid-conjugated liposomes for PET imaging of tumor angiogenesis

Introduction: We synthesized and evaluated Cu-64-labeled tetraiodothyroacetic acid (tetrac)-conjugated liposomes for PET imaging of tumor angiogenesis, because tetrac inhibits angiogenesis via integrin alpha v beta(3). 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 Cu-64 at 40 degrees C for 1 h and purified using a PD-10 column. Cu-64-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 degrees C. MicroPET imaging followed by tissue distribution study was carried out using U87MG tumor-bearing mice injected with tetrac/Cu-64-DOTA-liposomes or Cu-64-DOTA-liposomes. Results: HAEC binding studies exhibited that tetrac/Cu-64-DOTA-liposomes were avidly taken up by the cells from 1.02 %ID at 1 h to 11.89 %ID at 24 h, while Cu-64-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/Cu-64-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 2.70 036 %ID/g at 22 h. In contrast, tumor ROI analysis of 64Cu-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)CuDOTA-liposomes and Cu-64-DOTA-liposomes were 1.75 +/- 0.03 %ID/g and 036 +/- 0.01 %ID/g at 22 h, respectively. Conclusion: These results demonstrate that tetrac/Cu-64-DOTA-liposomes have significantly enhanced tumor uptake compared to Cu-64-DOTA-liposomes due to tetrac conjugation. Further studies are warranted to reduce the liver and spleen uptake of tetrac/Cu-64-DOTA-liposomes. (C) 2013 Elsevier Inc. All rights reserved.