title: Assessment of epidermal growth factor receptor with 99mTc-ethylenedicysteine-C225 monoclonal antibody.
abstract: Epidermal growth factor receptor (EGFR) plays an important role in cell division and cancer progression, as well as angiogenesis and metastasis. Since many tumor cells exhibit the EGFR on their surface, functional imaging of EGFR provides not only a non-invasive, reproducible, quantifiable alternative to biopsies, but it also greatly complements pharmacokinetic studies by correlating clinical responses with biological effects. Moreover, molecular endpoints of anti-EGFR therapy could be assessed effectively. C225 is a chimeric monoclonal antibody that targets the human extracellular EGFR and inhibits the growth of EGFR-expressing tumor cells. Also, it has been demonstrated that C225, in combination with chemotherapeutic drugs or radiotherapy, is effective in eradicating well-established tumors in nude mice. We have developed 99mTc-labeled C225 using ethylenedicysteine (EC) as a chelator. This study aimed at measuring uptake of 99mTc-EC-C225 in EGFR+ tumor-bearing animal models and preliminary feasibility of imaging patients with head and neck carcinomas. In vitro Western blot analysis and cytotoxicity assays were used to examine the integrity of EC-C225. Tissue distribution studies of 99mTc-EC-C225 were evaluated in tumor-bearing rodents at 0.5-4 h. In vivo biodistribution of 99mTc-EC-C225 in tumor-bearing rodents showed increased tumor-to-tissue ratios as a function of time. In vitro and biodistribution studies demonstrated the possibility of using 99mTc-EC-C225 to assess EGFR expression. SPECT images confirmed that the tumors could be visualized with 99mTc-EC-C225 from 0.5 to 4 h in tumor bearing rodents. We conclude that 99mTc-EC-C225 may be useful to assess tumor EGFR expression. This may be useful in the future for selecting patients for treatment with C225.
authors.affiliation: Division of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston 77030, USA.
authors.forename: Naomi R
authors.initials: NR
authors.lastname: Schechter
authors.forename: David J
authors.initials: DJ
authors.lastname: Yang
authors.forename: Ali
authors.initials: A
authors.lastname: Azhdarinia
authors.forename: Sahar
authors.initials: S
authors.lastname: Kohanim
authors.forename: Richard
authors.initials: R
authors.lastname: Wendt
authors.forename: Chang-Sok
authors.initials: CS
authors.lastname: Oh
authors.forename: Mickey
authors.initials: M
authors.lastname: Hu
authors.forename: Dong-Fang
authors.initials: DF
authors.lastname: Yu
authors.forename: Jerry
authors.initials: J
authors.lastname: Bryant
authors.forename: K Kian
authors.initials: KK
authors.lastname: Ang
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Forster
authors.forename: E Edmund
authors.initials: EE
authors.lastname: Kim
authors.forename: Donald A
authors.initials: DA
authors.lastname: Podoloff
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis / Q000378:metabolism*; D061067:Antibodies, Monoclonal, Humanized; D001943:Breast Neoplasms / Q000378:metabolism; D002460:Cell Line; D000068818:Cetuximab; D003545:Cysteine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism*; D066246:ErbB Receptors / Q000032:analysis / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D051381:Rats; D013667:Technetium / Q000032:analysis / Q000378:metabolism*; D014018:Tissue Distribution / Q000502:physiology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C109063:ethylene dicysteine; D013667:Technetium; D066246:ErbB Receptors; D003545:Cysteine; D000068818:Cetuximab