In vitro and in vivo behavior of radiolabeled chimeric anti-EGFRvIII monoclonal antibody: comparison with its murine parent.
Nucl Med Biol
; 24(7): 639-47, 1997 Oct.
Article
in En
| MEDLINE
| ID: mdl-9352535
ABSTRACT
The mutant version of the epidermal growth factor receptor EGFRvIII has been found on gliomas and other tumors, but not on normal tissues. Radioiodinated murine (mu) L8A4 monoclonal antibody (MAb) specifically targets EGFRvIII xenografts in vivo when labeled using N-succinimidyl 5-iodo-3-pyridinecarboxylate (SIPC). A chimeric (ch) MAb consisting of the variable region of muL8A4 and the constant domains of human IgG2 has been developed that has an affinity and radioiodinated immunoreactive fraction comparable to muL8A4. In vitro, both MAbs were internalized and processed by EGFRvIII expressing cell lines (U87MG delta EGFR or NR6M) at similar rates (maximum intracellular retention, 35-40%). In paired-label tissue distribution studies in athymic mice bearing U87MG delta EGFR tumor xenografts, the chmu L8A4 uptake ratio in normal tissues rose to greater than 21, whereas in tumor, the ratio remained 11 throughout the experiment. These results indicate that chL8A4 exhibits similar binding and internalization properties as its murine parent, but suggest different intracellular processing and/or deposition of catabolites in normal tissues for chL8A4.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Recombinant Fusion Proteins
/
ErbB Receptors
/
Antibodies, Monoclonal
Limits:
Animals
/
Humans
Language:
En
Journal:
Nucl Med Biol
Journal subject:
BIOLOGIA
/
MEDICINA NUCLEAR
Year:
1997
Document type:
Article
Affiliation country:
Estados Unidos