title: PET imaging of EGF receptors using [18F]FBEM-EGF in a head and neck squamous cell carcinoma model.
abstract: OBJECTIVE
  To prepare and evaluate a new radiotracer for molecular imaging of cell surface receptors for epidermal growth factor (EGF).
  
  
  METHODS
  Cys-tagged EGF (cEGF) was labeled with (18)F by coupling the free thiol group of the Cys tag with N-[2-(4-[(18)F]fluorobenzamido)ethyl]maleimide ([(18)F]FBEM) to form [(18)F]FBEM-cEGF. Cell uptake, internalization and efflux of [(18)F]FBEM-cEGF were tested in human head and neck squamous carcinoma UM-SCC1 cells. In vivo tumor targeting and pharmacokinetics of the radiotracers were evaluated in UM-SCC1 tumor-bearing athymic nude mice by static and dynamic microPET imaging. Ex vivo biodistribution assays were performed to confirm the noninvasive imaging results.
  
  
  RESULTS
  The radiolabeling yield for [(18)F]FBEM-cEGF was over 60%, based on starting [(18)F]FBEM. [(18)F]FBEM-cEGF exhibited rapid blood clearance through both hepatobiliary and renal excretion. UM-SCC1 tumors were clearly visualized and showed modest tracer uptake of 2.60 ± 0.59 %ID/g at 30 min after injection. Significantly higher tumor uptake of [(18)F]FBEM-cEGF (5.99 ± 1.61%ID/g at 30 min after injection, p < 0.01) and tumor/nontumor ratio were achieved by coinjection of 50 μg of unlabeled EGF. Decreased liver uptake of [(18)F]FBEM-cEGF was observed when unlabeled EGF was coadministered.
  
  
  CONCLUSIONS
  With optimized liver blocking, [(18)F]FBEM-cEGF has the potential to be used in a noninvasive and quantitative manner for detection of malignant lesions and evaluation of EGFR activity.
authors: Department of Medical Imaging and Nuclear Medicine, Fourth Affiliated Hospital, Harbin Medical University, 37 Yinhang Street, Nangang District, Harbin 150001, China.
authors: Weihua
authors: W
authors: Li
authors: Gang
authors: G
authors: Niu
authors: Lixin
authors: L
authors: Lang
authors: Ning
authors: N
authors: Guo
authors: Ying
authors: Y
authors: Ma
authors: Dale O
authors: DO
authors: Kiesewetter
authors: Joseph M
authors: JM
authors: Backer
authors: Baozhong
authors: B
authors: Shen
authors: Xiaoyuan
authors: X
authors: Chen
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000473:pathology; D045744:Cell Line, Tumor; D003545:Cysteine / Q000737:chemistry; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D005462:Fluorine Radioisotopes / Q000494:pharmacology*; D006258:Head and Neck Neoplasms / Q000175:diagnosis* / Q000473:pathology; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D008301:Maleimides / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D008956:Models, Chemical; D064847:Multimodal Imaging / Q000379:methods; D009368:Neoplasm Transplantation; D049268:Positron-Emission Tomography / Q000379:methods; D013997:Time Factors; D014018:Tissue Distribution; D014057:Tomography, X-Ray Computed
chemical_list: D005462:Fluorine Radioisotopes; D008301:Maleimides; C512447:N-(2-(4-18F-fluorobenzamido)ethyl)maleimide; D066246:ErbB Receptors; D003545:Cysteine