title: Monoclonal antibodies for copper-64 PET dosimetry and radioimmunotherapy.
abstract: BACKGROUND
  We previously described a two-antibody model of (64)Cu radioimmunotherapy to evaluate low-dose, solid-tumor response. This model was designed to test the hypothesis that cellular internalization is critical in causing tumor cell death by mechanisms in addition to radiation damage. The purpose of the present study was to estimate radiation dosimetry for both antibodies (mAbs) using positron emission tomography (PET) imaging, and evaluate the effect of internalization on tumor growth.
  
  
  RESULTS
  Dosimetry was similar between therapy groups. Median time to tumor progression to 1 g ranged from 7 to 12 days for control groups and was 32 days for both treatment groups (p < 0.0001). No statistically significant difference existed between any control group or between the treatment groups.
  
  
  METHODS
  In female nude mice bearing LS174T colon carcinoma xenografts, tumor dosimetry was calculated using serial PET images of three mice in each group of either internalizing (64)Cu-labeled DOTA-cBR96 (DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) or non-internalizing (64)Cu-labeled DOTA-cT84.66 from 3 to 48 h. For the therapy study, controls (n = 10) received saline, DOTA-cBR96, or DOTA-cT84.66. Treatment animals (n = 9) received 0.890 mCi of (64)Cu-labeled DOTA-cBR96 or 0.710 mCi of (64)Cu-labeled DOTA-cT84.66. Tumors were measured daily.
  
  
  CONCLUSIONS
  PET imaging allows the use of (64)Cu for pre-therapy calculation of tumor dosimetry. In spite of highly similar tumor dosimetry, an internalizing antibody did not improve the outcome of (64)Cu radioimmunotherapy. Radioresistance of this tumor cell line and copper efflux may have confounded the study. Further investigations of the 2 therapeutic efficacy of (64)Cu-labeled mAbs will focus on interaction between (64)Cu and tumor suppressor genes and copper chaperones.
authors.affiliation: Department of Veterinary Medicine and Surgery, University of Missouri-Columbia, USA.
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Bryan
authors.forename: Fang
authors.initials: F
authors.lastname: Jia
authors.forename: Huma
authors.initials: H
authors.lastname: Mohsin
authors.forename: Geethapriya
authors.initials: G
authors.lastname: Sivaguru
authors.forename: Carolyn J
authors.initials: CJ
authors.lastname: Anderson
authors.forename: William H
authors.initials: WH
authors.lastname: Miller
authors.forename: Carolyn J
authors.initials: CJ
authors.lastname: Henry
authors.forename: Michael R
authors.initials: MR
authors.lastname: Lewis
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy; D003301:Copper Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D049268:Positron-Emission Tomography; D016499:Radioimmunotherapy; D016019:Survival Analysis; D014018:Tissue Distribution; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D003301:Copper Radioisotopes