Comparison of IgG and F(ab')2 fragments of bispecific anti-RCCxanti-DTIn-1 antibody for pretargeting purposes.
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.
van Schaijk
Frank G
FG
Department of Nuclear Medicine, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. F.vanSchaijk@nucmed.umcn.nl
Boerman
Otto C
OC
Soede
Annemieke C
AC
McBride
William J
WJ
Goldenberg
David M
DM
Corstens
Frans H M
FH
Oosterwijk
Egbert
E
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
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D007205:Indium Radioisotopes; D019275:Radiopharmaceuticals