Biodistribution and radioimmunotherapy of SCCHN in xenotransplantated SCID mice with a 131I-labelled anti-EpCAM monoclonal antibody.
BACKGROUND
The mortality from squamous cell carcinoma of the head and neck (SCCHN) remains high and almost unchanged throughout the last decades. Therefore, new therapeutic strategies are urgently needed. One promising approach is the application of radio-labeled antibodies directed against tumor-associated antigens. EpCAM is a transmembrane protein, which is overexpressed on almost all SCCHN, making it a suitable anchor molecule for targeted radioimmunotherapy (RIT). The aim of this study was to establish an animal model to investigate the biodistribution and the therapeutic effect of a radio-labeled EpCAM-specific monoclonal antibody (mAb).


METHODS
The mAb C215 was labeled with 131I and tested for its antitumor effect against established SCCHN xenografts in SCID mice. Initially, the biodistribution of the mAb in the tumor and different organs was determined with a gamma counter and was calculated as % injected dose/gram tissue. For therapeutic approaches 5, 15 or 25 MBq 131I-labeled mAb was injected as a single bolus into tumor-bearing mice. Control animals received either sodium chloride or the unlabeled mAb. The tumor growth and body weight of the animals were measured at various times after administration of the antibody.


RESULTS
Initially, high activity was seen in all organs after systemic administration of 13I-C215. Over time general activity decreased whereas an accumulation of activity was seen in the tumor. Tumor growth was delayed in the groups receiving either 15 MBq or 25 MBq 131I-C215 relative to control groups and the 5 MBq group. However, animals in the high-dose groups suffered from treatment-related toxicity, which led to body weight loss of more than 20%.


CONCLUSIONS
Our data demonstrate that the EpCAM-specific radio-labeled mAb C215 is a promising tool to target SCCHN leading to significant tumor control. Further studies are necessary to increase efficacy and reduce toxicity of this new therapeutic approach.
Andratschke
Michaela
M
Department of Otorhinolaryngology, Head and Neck Surgery, Ludwig-Maximilians-University of Munich, Germany. Michaela.Andratschke@hno.uni-luebeck.de
Gildehaus
Franz Josef
FJ
Johannson
Veronika
V
Schmitt
Baerbel
B
Mack
Brigitte
B
Reisbach
Gilbert
G
Lang
Stephan
S
Lindhofer
Horst
H
Zeidler
Reinhard
R
Wollenberg
Barbara
B
Luebbers
Christian W
CW
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000493:pharmacokinetics / Q000494:pharmacology*; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000276:immunology*; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000378:metabolism / Q000532:radiotherapy*; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000276:immunology*; D000071858:Epithelial Cell Adhesion Molecule; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000276:immunology / Q000378:metabolism / Q000532:radiotherapy*; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism; D000922:Immunotoxins / Q000276:immunology / Q000493:pharmacokinetics / Q000494:pharmacology*; D007457:Iodine Radioisotopes / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D016499:Radioimmunotherapy / Q000379:methods*; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; D007074:Immunoglobulin G; D000922:Immunotoxins; D007457:Iodine Radioisotopes