Localization of 131I-labelled monoclonal antibody ERIC1 in a subcutaneous xenograft model of neuroblastoma in SCID mice.
OBJECTIVE
To evaluate a novel strategy of immunolocalization of human neuroblastoma by targeting the neural cell adhesion molecule (NCAM), which is over-expressed on neuroblastoma.


METHODS
NCAM expression on the cell surface of established neuroblastoma cells was shown by flow cytometry. A SCID mouse model using IMR5-75 neuroblastoma cells to induce subcutaneous tumour growth was established. 131I was used to label monoclonal NCAM specific ERIC1 antibodies generating the 131I-ERIC1 antibody, which showed a high affinity to NCAM also after labelling (KD=9 x 10(-8) mol . l(-1)).


RESULTS
Measurement of organ-specific radioactivity showed low organ-specific uptake (5.33%ID/g (percent of injected dose per gram of tissue) after 72 h), which continuously decreased over the 96 h investigation period, demonstrating clearance of radioactivity. In contrast, tumours accumulated radioactivity continuously up to a peak of 42.07%ID/g at the 96 h time point (31.07%ID/g at 72 h). This specific uptake could be blocked by application of unlabelled ERIC1 antibodies. Measurement of blood specific radioactivity revealed a characteristic clearance over the first 72 h. With 37 Gy, tumour-specific radioactivity reached therapeutic doses after 96 h.


CONCLUSIONS
These results indicate that 131I-labelled ERIC1 has the ability to probe NCAM-expressing tumour cells in vivo with high efficiency and is a promising reagent for the diagnosis and treatment of NCAM-positive human tumours, especially for neuroblastoma.
Otto
Christina
C
Department of Nuclear Medicine, University of Cologne, Germany.
Jensen
Markus
M
Dietlein
Markus
M
Fischer
Thomas
T
Schmidt
Matthias
M
Tawadros
Samir
S
Börner
Sarah Maria
SM
Weber
Sebastian Alfred
SA
Spitz
Rüdiger
R
Bloch
Wilhelm
W
Berthold
Frank
F
Schicha
Harald
H
Schomäcker
Klaus
K
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008657:Metabolic Clearance Rate; D051379:Mice; D016513:Mice, SCID; D019006:Neural Cell Adhesion Molecules / Q000276:immunology / Q000378:metabolism*; D009447:Neuroblastoma / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000532:radiotherapy; D009928:Organ Specificity; D016499:Radioimmunotherapy / Q000379:methods; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics / Q000627:therapeutic use; D014018:Tissue Distribution; D014915:Whole-Body Counting
D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes; D019006:Neural Cell Adhesion Molecules; D019275:Radiopharmaceuticals