Issue 24, 2008
From the journal:

Dalton Transactions

Rhenium and technetium complexes bearing quinazoline derivatives: progress towards a 99mTc biomarker for EGFR-TK imaging†

Célia Fernandes,a   Isabel C. Santos,a   I. Santos,*a   Hans-Jurgen Pietzsch,b   Jens-Uwe Kunstler,b   Werner Kraus,c   Ana Rey,d   Nikos Margaritis,e   Athanasia Bourkoula,e   Aris Chiotellis,e   Maria Paravatou-Petsotase  and  Ioannis Pirmettise  

* Corresponding authors

a Departamento de Química, ITN, Estrada Nacional 10, Sacavém Codex, Portugal
E-mail: isantos@itn.pt

b Institute of Radiopharmacy, Forschungszentrum Dresden-Rossendorf, P.O.B. 510 119, Dresden, Germany

c Federal Institute for Materials Research and Testing (BAM), Berlin, Germany

d Radiochemistry Department, Faculty of Chemistry, Universidad de la Republica, Montevideo, Uruguay

e Institute of Radioisotopes - Radiodiagnostic Products, National Centre for Scientific Research “Demokritos”, Athens, Greece

Abstract

The quinazoline derivatives (3-chloro-4-fluorophenyl)quinazoline-4,6-diamine (2) and (3-bromophenyl)quinazoline-4,6-diamine (3) were labelled with 99mTc using the “4 + 1” mixed-ligand system [Tc(NS3)(CN-R)] and the tricarbonyl moiety fac-[Tc(CO)3]+. In the “4 + 1” approach the technetium(III) is stabilized by a monodentate isocyanide bearing a quinazoline fragment (L11, L22) and by the tetradentate tripodal ligand tris(2-mercaptoethyl)-amine (NS3). In the “4 + 1” approach, 99mTc-labelling was performed in a two-step procedure, the complexes [Tc(NS3)(L11)] (7a) and [Tc(NS3)(L22)] (8a) being obtained in about 50–70% yield. In the tricarbonyl approach, the fac-[Tc(CO)3]+ unit is anchored by two different monoanionic chelators bearing the quinazoline derivatives (3-chloro-4-fluorophenyl)quinazoline-4,6-diamine (2) and (3-bromophenyl)quinazoline-4,6-diamine (3). Both chelators have a N2O donor atom set, but one contains a pyrazolyl ring (L55H) and the other contains a pyridine unit (L66H). In both cases the conjugation of the quinazoline to the chelator was done through the secondary amine of the potentially tridentate and monoanionic chelators, the corresponding 99mTc-complexes (10a, 11a) being obtained in quantitative yield. The identities of the 99mTc-labelled quinazolines (7a, 8a, 10a, 11a) were confirmed by comparison with the HPLC profiles of the analogous Re compounds (7, 8, 10, 11). All these Re complexes were characterized by NMR and IR spectroscopy, elemental analysis and in some cases by MS and X-ray diffraction analysis. In vitro studies indicate that the quinazoline fragments, after conjugation to the cyano group (L11, L22) or to the pyrazolyl containing chelator (L55H), as well as the corresponding Re complexes (7, 8, 10) inhibit significantly the EGFR autophosphorylation and also inhibit A431 cell growth. These two effects were also found for the pyridine-containing chelator (L66H) and corresponding Re complex (11), although to a lesser extent.

Graphical abstract: Rhenium and technetium complexes bearing quinazoline derivatives: progress towards a 99mTc biomarker for EGFR-TK imaging

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Article information

DOI
https://doi.org/10.1039/B802021C
Article type
Paper
Submitted
04 Feb 2008
Accepted
01 Apr 2008
First published
13 May 2008

Dalton Trans., 2008, 3215-3225

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Rhenium and technetium complexes bearing quinazoline derivatives: progress towards a 99mTc biomarker for EGFR-TK imaging

C. Fernandes, I. C. Santos, I. Santos, H. Pietzsch, J. Kunstler, W. Kraus, A. Rey, N. Margaritis, A. Bourkoula, A. Chiotellis, M. Paravatou-Petsotas and I. Pirmettis, Dalton Trans., 2008, 3215 DOI: 10.1039/B802021C

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