title: In vitro and in vivo characterization of 177Lu-huA33: a radioimmunoconjugate against colorectal cancer.
abstract: BACKGROUND
  The humanized monoclonal antibody A33 (huA33) is a potential targeting agent against colorectal carcinoma since the A33 antigen is highly and homogenously expressed in >95% of all colorectal cancers, both primary tumors and metastases. The aim of this study was to determine the biodistribution and tumor-targeting ability of (177)Lu-labeled huA33.
  
  
  METHODS
  huA33 was labeled with the beta-emitting therapeutic nuclide (177)Lu using the chelator CHX-A"-DTPA, and the properties of the (177)Lu-CHX-A"-huA33 ((177)Lu-huA33) conjugate was determined both in vitro and in vivo in a biodistribution study in nude mice xenografted with colorectal SW1222 tumor cells.
  
  
  RESULTS
  The (177)Lu-huA33 conjugate bound specifically to colorectal cancer cells in vitro (with a K(D) value of 2.3+/-0.3 nM, determined by a saturation assay) and in vivo. The tumor uptake of (177)Lu-huA33 was very high, peaking at 134+/-21%ID/g 72 h postinjection (pi). Normal tissue uptake was low; radioactivity concentration in blood (which had the second highest radioactivity concentration) was lower than in tumor at all time points studied (8 h to 10 days). The tumor-to-blood ratio increased with time, reaching 70+/-30, 10 days pi. Throughout the study, the uptake of (177)Lu in bone (known to accumulate free (177)Lu) was low, and the fraction of protein-bound (177)Lu in plasma samples was high (95% to 99%). This indicates high stability of the (177)Lu-huA33 conjugate in vivo.
  
  
  CONCLUSIONS
  The (177)Lu-huA33 conjugate shows a very favorable biodistribution, with an impressively high tumor uptake and high tumor-to-organ ratios, indicating that the conjugate may be suitable for radioimmunotherapy of colorectal cancer.
authors.affiliation: Division of Radiology, Department of Oncology, Radiology, and Clinical Immunology, Uppsala University, Uppsala, Sweden. ylva.almqvist@radiol.uu.se <ylva.almqvist@radiol.uu.se>
authors.forename: Ylva
authors.initials: Y
authors.lastname: Almqvist
authors.forename: Ann-Charlott
authors.initials: AC
authors.lastname: Steffen
authors.forename: Vladimir
authors.initials: V
authors.lastname: Tolmachev
authors.forename: Chaitanya R
authors.initials: CR
authors.lastname: Divgi
authors.forename: Anders
authors.initials: A
authors.lastname: Sundin
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000532:radiotherapy*; D004355:Drug Stability; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000493:pharmacokinetics / Q000627:therapeutic use*; D008187:Lutetium / Q000627:therapeutic use*; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016499:Radioimmunotherapy; D011868:Radioisotopes / Q000627:therapeutic use*; D014018:Tissue Distribution
chemical_list: D000911:Antibodies, Monoclonal; C104258:GPA33 protein, human; D018796:Immunoconjugates; D008562:Membrane Glycoproteins; D011868:Radioisotopes; D008187:Lutetium