Novel estradiol based metal complexes of Tc-99m

Unidade de Ciências Químicas e Radiofarmacêuticas, Instituto Tecnológico e Nuclear, Instituto Superior Técnico, Universidade Técnica de Lisboa, Estrada Nacional 10, Sacavém, Portugal.
Journal of inorganic biochemistry (Impact Factor: 3.27). 03/2012; 111:1-9. DOI: 10.1016/j.jinorgbio.2012.03.001
Source: PubMed

ABSTRACT Aiming to contribute to the design of technetium imaging agents for estrogen receptor (ER) positive breast tumors, we have synthesized and evaluated the novel organometallic estradiol complexes (fac-[M(CO)(3)(κ(3)-10)](+) and fac-[M(CO)(3)(κ(3)-12) M=Re/(99m)Tc) using two different bifunctional tridentate ligands (4 and 8). The rhenium complexes (13 and 14) were fully characterized by IR, (1)H NMR, (13)C NMR, mass spectrometry and elemental analyses. The (99m)Tc complexes (15 and 16) were obtained with high radiochemical purity and exhibited high in vitro radiochemical stability. To get a first insight into the relevance of these complexes for targeting ER positive tumors, ER binding affinity assays and cellular internalization studies in an ER expressing cell line, MCF-7, have also been performed suggesting a non ER mediated uptake.


Available from: Maria Cristina das Neves Oliveira, Feb 25, 2015
1 Follower
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Recent advances (during the 2007-2014 period) in the coordination and organometallic chemistry of compounds containing natural and artificially prepared radionuclides (actinides and technetium), are reviewed. Radioactive isotopes of naturally stable elements are not included for discussion in this work. Actinide and technetium complexes with O-, N-, N,O, N,S-, P-containing ligands, as well π-organometallics are discussed from the view point of their synthesis, properties, and main applications. On the basis of their properties, several mono-, bi-, tri-, tetra- or polydentate ligands have been designed for specific recognition of some particular radionuclides, and can be used in the processes of nuclear waste remediation, i.e., recycling of nuclear fuel and the separation of actinides and fission products from waste solutions or for analytical determination of actinides in solutions; actinide metal complexes are also usefulas catalysts forcoupling gaseous carbon monoxide,as well as antimicrobial and anti-fungi agents due to their biological activity. Radioactive labeling based on the short-lived metastable nuclide technetium-99m (99mTc) for biomedical use as heart, lung, kidney, bone, brain, liver or cancer imaging agents is also discussed. Finally, the promising applications of technetium labeling of nanomaterials, with potential applications as drug transport and delivery vehicles, radiotherapeutic agents or radiotracers for monitoring metabolic pathways, are also described.
    Molecules 08/2014; 19(8):10755-802. DOI:10.3390/molecules190810755 · 2.10 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In recent years, the remarkable characteristics of the organometallic precursor fac-[M(CO)3(H2O)3]+ (M = Re, Tc) introduced by Alberto and co-workers brought renewed interest to the development of low-oxidation 99mTc-based radioactive probes. Considering our interest in the design of target-specific radioactive probes for SPECT-imaging and targeted systemic radiotherapy, we have been involved in the study of the chemistry of fac-[M(CO)3]+ (M = Re, Tc) with chelators combining a pyrazolyl unit with aliphatic amines and/or carboxylic acids or thioethers. This review describes our research efforts in the field, giving particular emphasis to the biological properties of Re(I) and 99mTc(I) complexes anchored by those type of chelators. We aim to highlight the versatility of the pyrazolyl-containing chelators, which allowed the successful labeling of a wide range of relevant biomolecules, spanning from small lipophilic organic molecules, such as quinazoline derivatives or DNA-binders, to tumor-seeking peptides for in vivo receptor targeting. Noteworthy is also the possibility of labeling polymeric nanoparticles based on dextran for sentinel lymph node detection (SLND), which has been one of our most successful achievements in recent years. These radiolabeled nanoparticles allowed the visualization of the SLN accurately at the preclinical level.
    Journal of Organometallic Chemistry 06/2013; 744. DOI:10.1016/j.jorganchem.2013.05.050 · 2.30 Impact Factor
  • Source
    Chemical Reviews 08/2013; 113(10). DOI:10.1021/cr400269j · 45.66 Impact Factor