title: EGF receptor targeted tumor imaging with biotin-PEG-EGF linked to (99m)Tc-HYNIC labeled avidin and streptavidin.
abstract: BACKGROUND
  As direct radiolabeled peptides suffer limitations for in vivo imaging, we investigated the usefulness of radioloabeled avidin and streptavidin as cores to link peptide ligands for targeted tumor imaging.
  
  
  METHODS
  Human epidermal growth factor (EGF) was site specifically conjugated with a single PEG-biotin molecule and linked to (99m)Tc-HYNIC labeled avidin-FITC (Av) or streptavidin-Cy5.5 (Sav). Receptor targeting was verified in vitro, and in vivo pharmacokinetic and biodistribution profiles were studied in normal mice. Scintigraphic imaging was performed in MDA-MB-468 breast tumor xenografted nude mice.
  
  
  RESULTS
  Whereas both (99m)Tc-Av-EGF and (99m)Tc-Sav-EGF retained receptor-specific binding in vitro, the two probes substantially diverged in pharmacokinetic and biodistribution behavior in vivo. (99m)Tc-Av-EGF was rapidly eliminated from the circulation with a T1/2 of 4.3 min, and showed intense hepatic accumulation but poor tumor uptake (0.6%ID/gm at 4 h). (99m)Tc-Sav-EGF displayed favorable in vivo profiles of longer circulation (T1/2β, 51.5 min) and lower nonspecific uptake that resulted in higher tumor uptake (3.8 %ID/gm) and clear tumor visualization at 15 h.
  
  
  CONCLUSIONS
  (99m)Tc-HYNIC labeled streptavidin linked with growth factor peptides may be useful as a protein-ligand complex for targeted imaging of tumor receptors.
authors: Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Kyung-Ho
authors: KH
authors: Jung
authors: Jin Won
authors: JW
authors: Park
authors: Jin-Young
authors: JY
authors: Paik
authors: Cung Hoa Thien
authors: CH
authors: Quach
authors: Yearn Seong
authors: YS
authors: Choe
authors: Kyung-Han
authors: KH
authors: Lee
mesh_terms: D000818:Animals; D001360:Avidin / Q000737:chemistry / Q000378:metabolism*; D001710:Biotin / Q000378:metabolism*; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D003952:Diagnostic Imaging / Q000379:methods*; D004815:Epidermal Growth Factor / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D015609:Organotechnetium Compounds / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D011092:Polyethylene Glycols / Q000737:chemistry; D011487:Protein Conformation; D011877:Radionuclide Imaging; D019809:Streptavidin / Q000737:chemistry / Q000378:metabolism*
chemical_list: D015609:Organotechnetium Compounds; C502075:technetium 99m HYNIC-human epidermal growth factor; D001360:Avidin; D011092:Polyethylene Glycols; D004815:Epidermal Growth Factor; D001710:Biotin; D019809:Streptavidin; D066246:ErbB Receptors