title: Evaluation of (111)In-labeled macrocyclic chelator-amino acid derivatives for cancer imaging.
abstract: OBJECTIVE
  We evaluated new (111)In-labeled amino acid derivatives, in which the amino acids are conjugated with1,4,7,10-tetra-azacyclododecane-1,4,7,10-tetraacetic acid (DOTA), 1,4,7,10-tetraazacyclododecane-1,7-diacetic acid (DO2A) or 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (DO3A).
  
  
  METHODS
  DOTA-aminoalanine (DOTA-A), DOTA-aminohomoalanine (DOTA-H), DOTA-lysine (DOTA-L), DO2A-alanine (DO2A-A), DO3A-alanine (DO3A-A) and DO3A-homoalanine (DO3A-H) were labeled with (111)In. In vitro cell uptake assays were performed usingHep3B (a human hepatoma cell line), CT26 (a mouse colon cancer cell line) and U87MG (a human glioma cell line). In vitro cell uptake inhibition assays were performed using U87MG and (111)In-DO3A-H. U87MG bearing xenografted mice were subject to biodistribution, SPECT imaging, autoradiography, and immunohistochemistry studies.
  
  
  RESULTS
  Of the amino acid derivatives and cell lines examined, U87MG and (111)In-DO3A-H showed highest uptake in vitro. This uptake was blocked by 2-aminobicyclo-[2,2,1] heptane-2-carboxylic acid (BCH) and by tryptophan. (111)In-DO3A-HSPECT imaging of U87MG bearing xenografted mice visualized tumors (mean tumor-to-muscle ratio 3.16±0.74). Autoradiography and immunohistochemistry revealed that (111)In-DO3A-H uptake matched L-type amino acid transporter 1 expression.
  
  
  CONCLUSIONS
  Tumor uptake was successfully imaged using (111)In-DO3A-H in U87MG bearing xenografted mice. (111)In-DO3A-H appears to be useful for imaging tumors expressing L-type amino acid transporter.
authors.affiliation: Department of Nuclear Medicine, Radiation Applied Life Science, Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul National University, Seoul 110-744, Korea.
authors.forename: Jong Jin
authors.initials: JJ
authors.lastname: Lee
authors.forename: Dinesh
authors.initials: D
authors.lastname: Shetty
authors.forename: Yun-Sang
authors.initials: YS
authors.lastname: Lee
authors.forename: Sang Eun
authors.initials: SE
authors.lastname: Kim
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Kim
authors.forename: Mi Kyung
authors.initials: MK
authors.lastname: Hong
authors.forename: Ji Yeon
authors.initials: JY
authors.lastname: Son
authors.forename: Jae Min
authors.initials: JM
authors.lastname: Jeong
mesh_terms: D000596:Amino Acids / Q000737:chemistry / Q000493:pharmacokinetics*; D000613:Aminobutyrates / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000737:chemistry / Q000493:pharmacokinetics; D005910:Glioma / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D007205:Indium Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D014183:Transplantation, Heterologous
chemical_list: C520644:1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid; C561329:1,4,7,10-tetraazacyclododecane-1,7-diacetic acid; D000596:Amino Acids; D000613:Aminobutyrates; D002614:Chelating Agents; D006573:Heterocyclic Compounds, 1-Ring; D007205:Indium Radioisotopes; D019275:Radiopharmaceuticals; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; C012223:alpha-aminobutyric acid