Radioimmuno targetting (99m)technetium labeled anti-epidermal growth factor receptor monoclonal antibodies in experimental tumor models.
OBJECTIVE
Monoclonal antibodies (MAb) directed at the extra cellular domain (ECD) of epidermal growth factor receptor (EGFR) offer a promising strategy for diagnosis and therapy of cancers that over-express EGFR. Radiolabelled MAbs against cell surface antigens have improved in vivo tumor diagnosis and treatment. EGFR over-expression has been reported in a wide range of carcinomas especially of the head and neck, breast, etc., and is associated with poor prognosis and resistance to therapy. CIBCNSH3 is a murine MAb generated to the ECD of EGFR in our laboratory and has been extensively characterized and has proven antitumor activity. The tumor targeting potential of (99m)Tc labelled CIBCNSH3 in an experimental tumor model is discussed in this paper.


METHODS
A431, an epidermoid carcinoma cell line with overexpression of EGFR, SUDHLH, a lymphoma cell line was used to induce xenografts in inbred adult female BALB/C mice and used for the study. A reduction mediated method of (99m)Tc labelling was adopted to label the MAb. Scintiscan pictures were taken at different time intervals after i.v. administration of the (99m)Tc labelled MAb using a gamma camera and results were correlated with those of biodistribution studies.


RESULTS
Immunoscan pictures taken at different time periods showed high uptake of the radioimmunoconjugate by the tumor providing clear tumor images and no uptake in control animals with lymphoma xenografts. Results of scan pictures correlated well with the biodistribution studies.


CONCLUSIONS
The radioimmunoconjugate (99m)Tc-CIBCNSH3 appears to be a promising tool in identifying any early recurrence and micro-metastasis of lesions that overexpress EGFR.
Meenakshi
A
A
Department of Biochemical Oncology, Cancer Institute (WIA), Regional Center for Cancer Research and Treatment of Government of India, Adyar, Chennai, India. meenakshi_a3@rediffmail.com
Ganesh
V
V
Suresh Kumar
R
R
Siva Kumar
N
N
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000493:pharmacokinetics*; D058846:Antibodies, Monoclonal, Murine-Derived; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging* / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006801:Humans; D007553:Isotope Labeling; D008223:Lymphoma / Q000000981:diagnostic imaging* / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009928:Organ Specificity; D015609:Organotechnetium Compounds / Q000276:immunology* / Q000493:pharmacokinetics*; D011863:Radioimmunoassay / Q000379:methods; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000276:immunology / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014915:Whole-Body Counting
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C485058:technetium Tc 99m CIBCNSH3; D066246:ErbB Receptors