André, João P.

Ferreira, Paula M. T.

Fontes, André Filipe Gomes Soares

Geraldes, Carlos F. G. C.

Prata, M. Isabel M.

Universidade do Minho: RepositoriUM

Acta of the International Symposia on Metal Complexes – ISMEC Acta, Volume 2 ISMEC 2012, June 18th – 22nd 2012 – Lisbon (Portugal)  1 Synthesis, in vitro and in vivo characterization of new chelator DO3AAHA and its derivate DO3AAHAPEG750  André FONTES, a) Paula M. FERREIRA, a) Maria I. M. PRATA, b) Carlos F. G. C. GERALDES, c) João P. ANDRÉ a)  a) Centro de Química, Universidade do Minho, Campus de Gualtar, Braga, Portugal; andre.fontes@quimica.uminho.pt b) Instituto de Ciências Nucleares Aplicadas à Saúde, Universidade de Coimbra, Pólo das Ciências da Saúde, Coimbra, Portugal c) Centro de Neurociências e Biologia Celular, Universidade de Coimbra, Coimbra, Portugal  Over the past years, a wide number of chelators has been synthetized in order to complex a diversity of metal ions useful in medical imaging. DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), is an adequate chelator for Gd(III) and Ga(III) due to the high kinetic and thermodynamic stabilities of the metal complexes (for MRI (magnetic resonance imaging) and PET (positron emission tomography) respectively) [1]. In this work, the DOTA-based chelator DO3AAHA (1,4,7,10-tetraazacyclododecane-1-(6-amino)hexanoic-4,7,10-triacetic acid – Figure 1a) was synthesized and characterized. DO3AAHA acts as a bifunctional chelator due to the pendant free amino group. This group can be easily conjugated to biomolecules such as peptides or anti-bodies [2]. The Gd(III) and Ga(III) complexes of these conjugates do not compromise the kinetic and thermodynamic stabilities in relation to those of the analogous DOTA chelates. In our first attempt to demonstrate the versatility and the advantages of DO3AAHA as a bifunctional chelator, it was attached to an activated PEG (polyethylene glycol) with Mn = 750, which afforded DO3AAHAPEG750 (1,4,7,10-tetraazacyclododecane-1-(6-amino(PEG750))hexanoic-4,7,10-triacetic acid – Figure 1b). Adding PEG units to chelating frameworks is known to improve the pharmacokinetic properties of the resulting chelates [3]. The relaxivity (r1 and r2) of the Gd(III) chelates of both ligands was measured at 20 MHz at 25 and 37 °C. The dependence of 1/T1 on the temperature and pH was also studied. The kinetic stability of [Gd(DO3AAHA)]- was confirmed performing a competition experiment with Zn2+. The biodistribution of the 67Ga-labeled chelates was investigated in Wistar rats.  Acta of the International Symposia on Metal Complexes – ISMEC Acta, Volume 2 ISMEC 2012, June 18th – 22nd 2012 – Lisbon (Portugal)  2 Submit the abstract online at your participant area (http://eventos.spq.pt/eventos/LoginSubAbstract.aspx), after completing the registration. You will be asked whether you wish to present an Oral Communication or a Poster. Due to the limited number of oral communications, the Scientific Committee will make a selection among all the submitted abstracts requesting oral presentation.  You also must choose whether or not you are interested in submitting a paper in Dalton Transactions. Also in this case, the number of papers allowed is limited. [one line spacing] Acknowledgements: FCT-Portugal and FEDER/COMPETE through CQ-UM and PhD grant of A. Fontes (SFRH/BD/63676/2009).  We include our contribution on topic: “Metal-based drugs: therapy and diagnosis.” 

Synthesis, in vitro and in vivo characterization of new chelator DO3AAHA and its derivate DO3AAHAPEG750

http://repositorium.sdum.uminho.pt/bitstream/1822/22027/4/Andr%c3%a9_abstract%20Lisboa.%20v2.pdf

Synthesis, in vitro and in vivo characterization of new chelator DO3AAHA and its derivate DO3AAHAPEG750

Abstract

Similar works

Full text

Available Versions

Universidade do Minho: RepositoriUM

Universidade do Minho: RepositoriUM