title: Evaluation of (64)Cu-labeled DOTA-D-Phe(1)-Tyr (3)-octreotide ((64)Cu-DOTA-TOC) for imaging somatostatin receptor-expressing tumors.
abstract: OBJECTIVE
  In-111 ((111)In)-labeled octreotide has been clinically used for imaging somatostatin receptor-positive tumors, and radiolabeled octreotide analogs for positron emission tomography (PET) have been developed. Cu-64 ((64)Cu; half-life, 12.7 h) is an attractive radionuclide for PET imaging and is produced with high specific activity using a small biomedical cyclotron. The aim of this study is to produce and fundamentally examine a (64)Cu-labeled octreotide analog, (64)Cu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-D: -Phe(1)-Tyr(3)-octreotide ((64)Cu-DOTA-TOC).
  
  
  METHODS
  (64)Cu produced using a biomedical cyclotron was reacted with DOTA-TOC for 30 min at 45 degrees C. The stability of (64)Cu-DOTA-TOC was evaluated in vitro (incubated with serum) and in vivo (blood collected after administration) by HPLC analysis. Biodistribution studies were performed in normal mice by administration of mixed solution of (64)Cu-DOTA-TOC and (111)In-DOTA-TOC and somatostatin receptor-positive U87MG tumor-bearing mice by administration of (64)Cu-DOTA-TOC or (64)Cu-1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic acid-octreotide ((64)Cu-TETA-OC). The tumor was imaged using (64)Cu-DOTA-TOC, (64)Cu-TETA-OC, and FDG with an animal PET scanner.
  
  
  RESULTS
  (64)Cu-DOTA-TOC can be produced in amounts sufficient for clinical study with high radiochemical yield. (64)Cu-DOTA-TOC was stable in vitro, but time-dependent transchelation to protein was observed after injection into mice. In biodistribution studies, the radioactivity of (64)Cu was higher than that of (111)In in all organs except kidney. In tumor-bearing mice, (64)Cu-DOTA-TOC showed a high accumulation in the tumor, and the tumor-to-blood ratio reached as high as 8.81 +/- 1.17 at 6 h after administration. (64)Cu-DOTA-TOC showed significantly higher accumulation in the tumor than (64)Cu-TETA-OC. (64)Cu-DOTA-TOC PET showed a very clear image of the tumor, which was comparable to that of (18)F-FDG PET and very similar to that of (64)Cu-TETA-OC.
  
  
  CONCLUSIONS
  (64)Cu-DOTA-TOC clearly imaged a somatostatin receptor-positive tumor and seemed to be a potential PET tracer in the clinical phase.
authors.affiliation: Department of Bioimaging Information Analysis, Gunma University Graduate School of Medicine, Showa-machi, Maebashi 371-8511, Japan. hhanaoka@med.gunma-u.ac.jp
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Hanaoka
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Tominaga
authors.forename: Keiich
authors.initials: K
authors.lastname: Yamada
authors.forename: Pramila
authors.initials: P
authors.lastname: Paudyal
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Iida
authors.forename: Shigeki
authors.initials: S
authors.lastname: Watanabe
authors.forename: Bishnuhari
authors.initials: B
authors.lastname: Paudyal
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Higuchi
authors.forename: Noboru
authors.initials: N
authors.lastname: Oriuchi
authors.forename: Keigo
authors.initials: K
authors.lastname: Endo
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003301:Copper Radioisotopes / Q000737:chemistry*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007553:Isotope Labeling; D051379:Mice; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism*; D015282:Octreotide / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D009942:Organometallic Compounds / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods*; D017481:Receptors, Somatostatin / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: C507387:111In-DOTA-TOC; D003301:Copper Radioisotopes; D009942:Organometallic Compounds; D017481:Receptors, Somatostatin; C421169:copper 1,4,8,11--tetraazacyclotetradecane-N,N',N'',N'''-tetraacetic acid-octreotide; D015282:Octreotide; C106246:Edotreotide