RESUMO
The Stille reaction with 4-[(18)F]fluoroiodobenzene as a novel approach for the synthesis of radiotracers for monitoring COX-2 expression by means of PET has been developed. Optimized reaction conditions were elaborated by screening of various catalyst systems and solvents. By using optimized reaction conditions (18)F-labelled COX-2 inhibitors [(18)F]-5 and [(18)F]-13 could be obtained in radiochemical yields of up to 94% and 68%, respectively, based upon 4-[(18)F]fluoroiodobenzene.
Assuntos
Inibidores de Ciclo-Oxigenase 2/síntese química , Radioisótopos de Flúor/química , Iodobenzenos/química , Tomografia por Emissão de Pósitrons/métodos , Inibidores de Ciclo-Oxigenase 2/química , Estrutura Molecular , Traçadores RadioativosRESUMO
The diagnosis and staging of breast cancer could be improved by the development of imaging radiopharmaceuticals that provide a noninvasive determination of the estrogen receptor status in the tumor cells. Toward this goal, we have synthesized a number of novel Re-containing 7alpha-substituted estradiol complexes. The introduction of the 7alpha side chain involves the alkylation of tetrahydropyranyloxy-protected 6-keto estradiol. The methods used to introduce the rhenium metal involve "3 + 1" and "4 + 1" mixed ligand complexes (2a-c and 5, respectively), tricarbonyl dithioether complexes (3), and the cyclopentadienyltricarbonylmetal organometallic system (4ab, 6, 7). These complexes showed binding affinities for the estrogen receptor (as high as 45% for the "3 + 1" complex 2c) when compared to the native ligand estradiol. The polarity of some complexes (4ab) was modified to improve biodistribution properties by introducing (poly)ether linkages into the 7alpha side chain (6, 7). These complexes provide a further refinement of our understanding of ligand structure-binding affinity correlations for the estrogen receptor, and they furnish the synthetic groundwork for the synthesis of the analogous Tc-99m complexes for evaluation as breast tumor imaging agents.