A pyrazolylamine-phosphonate monoester chelator for the fac-[M(CO)(3)](+) core (M = Re, Tc-99m): Synthesis, coordination properties and biological assessment


Aiming to develop new strategies for the labeling of hydroxyl-containing biomolecules with the organometallic core fac-[Tc-99m(CO)(3)](+), we have prepared a new model bifunctional chelator, L4 (ethyl hydrogen (2-{[2-(3,5-dimethyl-1H-pyrazol-1-yl)ethyl]amino}ethyl)phosphonate), combining a pyrazolyl-amine chelating group and a monophosphonate ethyl ester function (-P(O)OHOEt). The phosphonate group allows metal stabilization, and, simultaneously, can be considered as a potential attachment site for a biomolecule. Reaction of L4 with the precursor [Tc-99m(H2O)(3)(CO)(3)](+) gave the model radiocomplex [Tc-99m(CO)(3)(k(3)-L4)] (6a). This radiocomplex was identified by comparing its chromatographic profile with that of the corresponding Re analog (6) under the same conditions, also prepared and fully characterized by the usual analytical techniques. Radiocomplex 6a is moderately lipophilic (log P-o/w = 1.07), presenting high stability in vitro without any measurable decomposition or ligand exchange, even in the presence of strong competing chelators such as histidine and cysteine (37 degrees C, 24 h). Biodistribution studies of the complex in CD-1 mice indicated a rapid blood clearance, and a rapid clearance from main organs, occurring primarily through the hepatobiliary pathway. Complex 6a. presents also a high robustness in vivo, demonstrated by its resistance to metabolic degradation in blood, and intact excretion into the urine, after RP-HPLC analysis of blood and urine samples. Copyright (C) 2007 John Wiley & Sons, Ltd.



subject category

Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry


Palma, E; Oliveira, BL; Figueira, F; Correia, JDG; Raposinho, PD; Santos, I

our authors

Share this project:

Related Publications

We use cookies for marketing activities and to offer you a better experience. By clicking “Accept Cookies” you agree with our cookie policy. Read about how we use cookies by clicking "Privacy and Cookie Policy".