| Abstract |
This report describes the synthesis and biological evaluation of cationic Tc-99m-tricarbonyl complexes anchored by ether-containing tris(pyrazolyl)methane or bis(pyrazolyl)ethanamine ligands to be applied in the design of radiopharmaceuticals for myocardial imaging: fac-[Tc-99m(CO)(3)\RC(pz)(3)\](+)(R = H (1a), MeOCH2 (2a), EtOCH2 (3a), (PrOCH2)-Pr-n (4a)) and fac-[Tc-99m(CO)(3)\RNHCH2CH(pz)(2)\](+) (R = H (5a), MeO(CH2)(2) (6a)) ( pz = pyrazolyl). At the no carrier added level, complexes 1a-6a were obtained in high radiochemical yield (> 98\%) by reaction of fac-[Tc-99m(CO)(3)(H2O)(3)](+) with the corresponding tripod chelator in aqueous medium. All these complexes display a high in vitro and in vivo stability, except 6a which metabolizes in vivo yielding fac-[Tc-99m(CO)(3)\HO(CH2)(2)NHCH2CH(pz)(2)\](+) (7a). Biological studies in mice have shown that among the radiotracers evaluated in this work, 3a, anchored by a tris( pyrazolyl) methane chelator bearing an ethyl methyl ether substituent, has the highest heart uptake (3.6 +/- 0.5\% ID g(-1) at 60 min p.i.). Complex 3a presents also the best heart : blood, heart : liver and heart : lung ratios, appearing as the most promising as a potential myocardial imaging agent. The chemical identity of 1a-7a was ascertained by HPLC comparison with the previously reported fac-[Re(CO)(3)\HC(pz)(3)\]Br (1) and with the novel fac-[Re(CO)(3)\RC(pz)(3)\] Br ( R = MeOCH2 (2), EtOCH2 (3), (PrOCH2)-Pr-n(4)) and fac-[Re(CO)(3)\RNHCH2CH(pz)(2)\] Br (R = H (5), MeO(CH2)(2) (6) HO(CH2)(2) (7)). The novel Re(I) tricarbonyl complexes, 2-7, were characterized by the common analytical techniques, including single crystal X-ray diffraction analysis. The solid state structure con. rmed the presence of facial and tridentate (kappa(3)-N-3) anchor ligands. Solution NMR studies have also shown that this kappa(3)-N-3 coordination mode is retained in solution for all complexes (2-7). |
