title: 124I-huA33 antibody uptake is driven by A33 antigen concentration in tissues from colorectal cancer patients imaged by immuno-PET.
abstract: The primary aim of this analysis was to examine the quantitative features of antibody-antigen interactions in tumors and normal tissue after parenteral administration of antitumor antibodies to human patients.
  
  
  METHODS
  Humanized anti-A33 antibody (10 mg) labeled with the positron-emitting radionuclide (124)I ((124)I-huA33) was injected intravenously in 15 patients with colorectal cancer. Clinical PET/CT was performed approximately 1 wk later, followed by a detailed assay of surgically removed tissue specimens including radioactivity counting, autoradiography, immunohistochemistry, and antigen density determination.
  
  
  RESULTS
  PET/CT showed high levels of antibody targeting in tumors and normal bowel. In tissue specimens, the spatial distribution of (124)I-huA33 conformed to that of A33 antigen, and there was a linear relationship between the amount of bound antibody and antigen concentration. Antibody uptake was high in 1- to 2-mm regions of antigen-positive tumor cells (mean, ~0.05 percentage injected dose per gram) and in antigen-positive normal colonic mucosa (mean, ~0.03 percentage injected dose per gram). The estimated binding site occupancy for tumor and normal colon was 20%-50%.
  
  
  CONCLUSIONS
  The in vivo biodistribution of (124)I-huA33 in human patients 1 wk after antibody administration was determined by A33 antigen expression. Our data imply that the optimal strategy for A33-based radioimmunotherapy of colon cancer will consist of a multistep treatment using a radionuclide with short-range (α- or β-particle) emissions.
authors: Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
authors: Joseph A
authors: JA
authors: O'Donoghue
authors: Peter M
authors: PM
authors: Smith-Jones
authors: John L
authors: JL
authors: Humm
authors: Shutian
authors: S
authors: Ruan
authors: Daniel A
authors: DA
authors: Pryma
authors: Achim A
authors: AA
authors: Jungbluth
authors: Chaitanya R
authors: CR
authors: Divgi
authors: Jorge A
authors: JA
authors: Carrasquillo
authors: Neeta
authors: N
authors: Pandit-Taskar
authors: Yuman
authors: Y
authors: Fong
authors: Vivian E
authors: VE
authors: Strong
authors: Nancy E
authors: NE
authors: Kemeny
authors: Lloyd J
authors: LJ
authors: Old
authors: Steven M
authors: SM
authors: Larson
mesh_terms: D000368:Aged; D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000276:immunology / Q000378:metabolism*; D001345:Autoradiography; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging* / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology* / Q000378:metabolism*; D008875:Middle Aged; D064847:Multimodal Imaging; D049268:Positron-Emission Tomography; D021381:Protein Transport; D014057:Tomography, X-Ray Computed
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C104258:GPA33 protein, human; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins