title: 64Cu-Labeled tetraiodothyroacetic acid-conjugated liposomes for PET imaging of tumor angiogenesis.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.affiliation: 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.
authors.forename: Choong Mo
authors.initials: CM
authors.lastname: Kang
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Koo
authors.forename: Sangbin
authors.initials: S
authors.lastname: Lee
authors.forename: Kyo Chul
authors.initials: KC
authors.lastname: Lee
authors.forename: Yu-Kyoung
authors.initials: YK
authors.lastname: Oh
authors.forename: Yearn Seong
authors.initials: YS
authors.lastname: Choe
mesh_terms: D000818:Animals; D002417:Cattle; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D003301:Copper Radioisotopes; D004355:Drug Stability; D005909:Glioblastoma / Q000098:blood supply* / Q000473:pathology; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D008297:Male; D051379:Mice; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging*; D049268:Positron-Emission Tomography / Q000379:methods*; D013974:Thyroxine / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D003301:Copper Radioisotopes; D008081:Liposomes; C011126:tetraiodothyroacetic acid; D013974:Thyroxine
keywords: Angiogenesis; MicroPET; Tetrac/(64)Cu-DOTA-liposomes; Tumor imaging