title: Radioiodination of new EGFR inhibitors as potential SPECT agents for molecular imaging of breast cancer.
abstract: In our search for the development of novel SPECT radioligands for EGFR positive tumours, new potentially irreversible tyrosine kinase (TK) inhibitors are being explored. The radioiodination of N-{4-[(3-chloro-4-fluorophenyl) amino]quinazoline-6-yl}-3-bromopropionamide, a novel EGFR-TK inhibitor synthesised in our laboratory, was accomplished via halogen exchange. Purification by RP-HPLC gave [125I]-N-{4-[(3-chloro-4-fluorophenyl)amino]quinazoline-6-yl}-3-iodopropionamide with a radiochemical purity higher than 95% and a high specific activity. In vitro studies indicate that both iodinated quinazoline and its bromo precursor inhibit A431 cell growth and also possess higher potency than the parent quinazoline to inhibit the EGFR autophosphorylation. In vivo stability studies suggest metabolization of the radioiodinated quinazoline indicating a short biological half-life. The in vitro results point out that these quinazoline derivatives could be promising candidates for SPECT imaging of EGFR positive tumours provided that they are selectively modified in order to achieve better in vivo radiochemical stability.
authors: Departamento de Química, ITN, Estrada Nacional 10, 2686-953, Sacavém Codex, Portugal.
authors: Célia
authors: C
authors: Fernandes
authors: Cristina
authors: C
authors: Oliveira
authors: Lurdes
authors: L
authors: Gano
authors: Athanasia
authors: A
authors: Bourkoula
authors: Ioannis
authors: I
authors: Pirmettis
authors: Isabel
authors: I
authors: Santos
mesh_terms: D001798:Blood Proteins / Q000378:metabolism; D001943:Breast Neoplasms / Q000000981:diagnostic imaging*; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D007457:Iodine Radioisotopes / Q000737:chemistry*; D010766:Phosphorylation; D011799:Quinazolines / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D001798:Blood Proteins; D004791:Enzyme Inhibitors; D007457:Iodine Radioisotopes; D011799:Quinazolines; D066246:ErbB Receptors