title: [99mTc] HYNIC-hEGF, a potential agent for imaging of EGF receptors in vivo: preparation and pre-clinical evaluation.
abstract: Expression of epidermal growth factor receptors (EGFR) has prognostic and predictive value in many kinds of tumors. Imaging of expression of EGFR in vivo may give valuable diagnostic information. The epidermal growth factor (EGF), a natural ligand, is a possible candidate for the targeting of EGFR. The present study describes a method for preparation of (99m)Tc-EGF via the hydrazinopyridine-3-carboxylic acid (HYNIC) conjugation using tricine and ethylenediamine-N,N'-diacetic acid (EDDA) as co-ligands. Both conjugates bound EGFR expressing cells with nanomolar affinity, and demonstrated good intracellular retention. The complex with EDDA demonstrated much higher stability in blood serum and during cysteine challenge. Biodistribution of (99m)Tc-EDDA-HYNIC-EGF in normal mice demonstrated fast blood clearance of conjugate, and its ability to bind EGFR in vivo. (99m)Tc-EDDA-HYNIC-EGF is a promising candidate for visualization of EGFR expression in vivo.
authors.affiliation: Radioisotope Division, Nuclear Research Center, Atomic Energy Organisation of Iran, Tehran, Iran.
authors.forename: Mohammad Hossein
authors.initials: MH
authors.lastname: Babaei
authors.forename: Ylva
authors.initials: Y
authors.lastname: Almqvist
authors.forename: Anna
authors.initials: A
authors.lastname: Orlova
authors.forename: Mohammad
authors.initials: M
authors.lastname: Shafii
authors.forename: Kalevi
authors.initials: K
authors.lastname: Kairemo
authors.forename: Vladimir
authors.initials: V
authors.lastname: Tolmachev
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000493:pharmacokinetics; D004353:Drug Evaluation, Preclinical; D004492:Edetic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004815:Epidermal Growth Factor / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006801:Humans; D006834:Hydrazines / Q000493:pharmacokinetics; D008024:Ligands; D008657:Metabolic Clearance Rate; D051379:Mice; D009539:Nicotinic Acids / Q000493:pharmacokinetics; D017556:Technetium Compounds / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: C120392:6-hydrazinopyridine-3-carboxylic acid; D002614:Chelating Agents; D006834:Hydrazines; D008024:Ligands; D009539:Nicotinic Acids; D017556:Technetium Compounds; C026058:EDDA; D004815:Epidermal Growth Factor; D004492:Edetic Acid; D066246:ErbB Receptors