title: Gefitinib enhances radiotherapeutic effects of131I-hEGF targeted to EGFR by increasing tumor uptake of hEGF in tumor xenografts.
abstract: Gefitinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor which has been proven effective for cancer treatment. In this study, we sought to determine whether gefitinib could increase the in vivo tumor uptake of human131I-EGF (131I-hEGF), thereby enhancing the potential of hEGF as a vehicle for EGFR-targeted radionuclide therapy. Western blot analysis was conducted to detect the effects of gefitinib on EGFR expression in human head and neck squamous carcinoma cell line UM-SCC-22B. Nude mice bearing UM-SCC-22B tumor xenografts were pretreated via i.p. injection of gefitinib or DMSO (vehicle control), followed by i.v. injection of125I-hEGF; the animals were then subjected to ex vivo biodistribution or injection of131I-hEGF for planar γ-imaging using SPECT, respectively. Targeted radionuclide therapy using131I-hEGF combined with gefitinib as a vehicle targeting EGFR was also performed in UM-SCC-22B tumor xenografts. The EGFR level was unchangeable in cells pretreated with gefitinib, but after gefitinib pretreatment, the uptake of125I-hEGF in 22B tumor xenografts increased substantially while the uptake of125I-hEGF in normal organs was effectively unchanged.131I-hEGF as a vehicle for EGFR-targeting therapy combined with gefitinib therefore showed strong therapeutic effects against 22B tumor xenografts tolerant to gefitinib. The uptake of hEGF to EGFR-positive tumors was enhanced significantly after gefitinib pretreatment, suggesting that131I-hEGF is a potential vehicle for EGFR-targeting radionuclide therapy when combined with gefitinib.
authors.affiliation: Department of Nuclear Medicine, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Xia
authors.affiliation: Medical Isotopes Research Center, Peking University, Beijing, China.
authors.forename: He
authors.initials: H
authors.lastname: Peng
authors.affiliation: Department of Orthopedics, The Second Clinical Hospital of Lanzhou University, China.
authors.forename: Luo
authors.initials: L
authors.lastname: Zhiqiang
authors.affiliation: Department of Nuclear Medicine, Beijing Anzhen Hospital, Capital Medical University, Beijing, China. Electronic address: lxgf2222@163.com.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Xiaoli
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000627:therapeutic use*; D066246:ErbB Receptors / Q000378:metabolism*; D000077156:Gefitinib; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000528:radiation effects; D006258:Head and Neck Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude; D021381:Protein Transport / Q000187:drug effects; D011799:Quinazolines / Q000494:pharmacology*; D011836:Radiation Tolerance / Q000187:drug effects; D011854:Radiochemistry; D014018:Tissue Distribution / Q000187:drug effects
chemical_list: D007457:Iodine Radioisotopes; D011799:Quinazolines; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D000077156:Gefitinib
keywords: 131I; EGFR; Gefitinib; Radiotherapy; hEGF