title: Biodistributions of intact monoclonal antibodies and fragments of BLCA-38, a new prostate cancer directed antibody.
abstract: BACKGROUND
  Monoclonal antibodies (MAbs) are used for targeting agents to tumours while minimizing normal tissue exposure.
  
  
  METHODS
  A new anti-prostate cancer MAb, BLCA-38, was radioiodinated (I125) and assessed for its ability to target subcutaneous human prostate cancer (DU-145) xenografts after systemic intraperitoneal administration. For comparison, the profile of J591 MAb (now in clinical trial) against LNCaP-LN3 tumours was examined. Biodistribution profiles were obtained at various times, by assessing injected dose/gram (%ID/g) and xenograft to blood (X/B) ratios. Microautoradiography of xenografts was performed. After conjugation with a melittin peptide toxin, the profiles of BLCA-38 and J591 were compared with that of an irrelevant antibody, DS-1.
  
  
  RESULTS
  Xenograft localization by 125I-labeled BLCA-38 and J591 MAbs to their relevant antigen-positive tumors was comparable, and there was no unusual localization in nontumour tissues. F(ab')2 and Fab fragments gave improved X/B ratios, but the %ID/g xenograft was decreased and they accumulated in kidneys, bladder and stomach. In contrast, the conjugates of irrelevant antibody showed no tumour targeting. Microautoradiography showed more tumour accumulation of MAbs than F(ab')2s or Fabs.
  
  
  CONCLUSIONS
  BLCA-38 can target prostate cancer in vivo almost as effectively as J591. Given that J591 is used clinically, BLCA-38, which targets a different antigen, has potential for radioimmunoscintigraphy and for therapeutic targeting of prostate cancer.
authors.affiliation: School of Clinical Medicine, University of New South Wales, Sydney, Australia.
authors.forename: Teresa
authors.initials: T
authors.lastname: Carter
authors.forename: Katy
authors.initials: K
authors.lastname: Sterling-Levis
authors.forename: Kim
authors.initials: K
authors.lastname: Ow
authors.forename: Larissa
authors.initials: L
authors.lastname: Doughty
authors.forename: Meghan
authors.initials: M
authors.lastname: Hattarki
authors.forename: Deborah
authors.initials: D
authors.lastname: Shapira
authors.forename: Dean
authors.initials: D
authors.lastname: Hewish
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Kortt
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Russell
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D000912:Antibodies, Neoplasm / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D007140:Immunoglobulin Fab Fragments; D007274:Injections, Intraperitoneal; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D007668:Kidney / Q000378:metabolism; D008297:Male; D008555:Melitten / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010446:Peptide Fragments / Q000493:pharmacokinetics; D011471:Prostatic Neoplasms / Q000276:immunology*; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D001743:Urinary Bladder / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D007140:Immunoglobulin Fab Fragments; D007457:Iodine Radioisotopes; D010446:Peptide Fragments; D008555:Melitten