کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1396609 | 1501196 | 2009 | 7 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Synthesis and characterization of rhenium and technetium-99m tricarbonyl complexes bearing the 4-[3-bromophenyl]quinazoline moiety as a biomarker for EGFR-TK imaging Synthesis and characterization of rhenium and technetium-99m tricarbonyl complexes bearing the 4-[3-bromophenyl]quinazoline moiety as a biomarker for EGFR-TK imaging](/preview/png/1396609.png)
Aiming at the development of technetium-99m (99mTc) complexes for early detection and staging of EGFR positive tumors, the tyrosine kinase inhibitor 6-amino-4-[(3-bromophenyl)amino]quinazoline was derivatized with pyridine-2-carboxaldehyde to generate the imine 6-(pyridine-2-methylimine)-4-[(3-bromophenyl)amino]quinazoline suitable for reacting with the fac-[99mTc(CO)3]+ core as an N,N bidentate ligand.The labelling was performed in high yield (>90%) by ligand exchange reaction using fac-[99mTc(OH2)3(CO)3]+ as precursor. The 99mTc complex was characterized by comparative HPLC analysis using the analogous rhenium (Re) complex as reference. The Re complex was prepared by ligand exchange reaction using the fac-[ReBr3(CO)3]2− as precursor and was fully characterized by NMR and IR spectroscopies and elemental analysis. In vitro studies indicate that both the ligand and its Re complex inhibit the EGFR autophosphorylation (IC50: 17 ± 3.7 and 114 ± 23 nM respectively) in intact A431 cells, bind the receptor in a reversible mode, and inhibit A431 cell growth (IC50: 5.2 ± 1.1 and 2.0 ± 0.98 μM respectively). Biodistribution of the 99mTc complex in healthy animals showed a rather fast blood and soft tissue clearance between 1 and 15 min p.i. with excretion occurring mainly via the hepatobiliary system.
Aiming at the development of technetium-99m complexes for early detection and staging of EGFR positive tumors, the synthesis, characterization and evaluation of new rhenium and technetium-99m tricarbonyl complexes carrying the tyrosine kinase inhibitor 6-amino-4-[(3-bromophenyl)amino]quinazoline are reported.Figure optionsDownload as PowerPoint slide
Journal: European Journal of Medicinal Chemistry - Volume 44, Issue 10, October 2009, Pages 4021–4027