title: Comparison of IgG and F(ab')2 fragments of bispecific anti-RCCxanti-DTIn-1 antibody for pretargeting purposes.
abstract: OBJECTIVE
  An effective pretargeting strategy was developed for renal cell carcinoma (RCC) based on a biologically produced bispecific monoclonal antibody: anti-RCCxanti-DTPA(In) (bsMAb: G250xDTIn-1). Tumour uptake of a (111)In-labelled bivalent peptide after pretargeting with bsMAb G250xDTIn-1 was relatively high compared with that in other pretargeting systems using chemically coupled F(ab')(2) fragments. Here, we investigated the effect of the bsMAb form in the pretargeting strategy.
  
  
  METHODS
  To determine the optimal interval between the administration of each of the bsMAb forms and the (111)In-labelled bivalent peptide, the biodistribution of the radioiodinated bsMAb forms was studied in athymic mice with subcutaneous SK-RC-1 RCC tumours. Since tumour targeting of the radiolabelled peptide depends on the bsMAb form and dose, a bsMAb dose escalation study was carried out for both bsMAb forms. Under optimised conditions, the biodistribution of the (111)In label in mice with pretargeted RCC was determined from 4 h up to 7 days p.i.
  
  
  RESULTS
  The optimal interval between the two administrations was 72 h for the bsMAb IgG and 4 h for the bsMAb F(ab')(2). The optimal bsMAb dose for intact IgG was 67 pmol and the optimal bsMAb F(ab')(2) dose was 200 pmol. Targeting of the pretargeted RCC with 4 pmol (111)In-labelled bivalent peptide revealed high tumour uptake with both bsMAb forms.
  
  
  CONCLUSIONS
  With the pretargeting strategy, using either bsMAb IgG or bsMAb F(ab')(2), very efficient peptide targeting of the tumour was obtained. Uptake and retention of the radiolabel in the tumour with the pretargeting approach are not affected by the bsMAb form used.
authors.affiliation: Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. F.vanSchaijk@nucmed.umcn.nl
authors.forename: Frank G
authors.initials: FG
authors.lastname: van Schaijk
authors.forename: Otto C
authors.initials: OC
authors.lastname: Boerman
authors.forename: Annemieke C
authors.initials: AC
authors.lastname: Soede
authors.forename: William J
authors.initials: WJ
authors.lastname: McBride
authors.forename: David M
authors.initials: DM
authors.lastname: Goldenberg
authors.forename: Frans H M
authors.initials: FH
authors.lastname: Corstens
authors.forename: Egbert
authors.initials: E
authors.lastname: Oosterwijk
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology / Q000493:pharmacokinetics*; D002292:Carcinoma, Renal Cell / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000532:radiotherapy; D045744:Cell Line, Tumor; D004334:Drug Administration Schedule; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism*; D007074:Immunoglobulin G / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism*; D007205:Indium Radioisotopes / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008657:Metabolic Clearance Rate; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009928:Organ Specificity; D016499:Radioimmunotherapy / Q000379:methods; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics / Q000627:therapeutic use; D014018:Tissue Distribution
chemical_list: D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D007205:Indium Radioisotopes; D019275:Radiopharmaceuticals