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Dalton Transactions

The international journal for inorganic, organometallic and bioinorganic chemistry



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Dalton Trans., 2007, 3010 - 3019, DOI: 10.1039/b705226j

Rhenium and technetium tricarbonyl complexes anchored by pyrazole-based tripods: novel lead structures for the design of myocardial imaging agents

Leonor Maria, Susana Cunha, Margarida Videira, Lurdes Gano, António Paulo, Isabel C. Santos and Isabel Santos

This report describes the synthesis and biological evaluation of cationic 99mTc–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-[99mTc(CO)3{RC(pz)3}]+ (R = H ( 1a), MeOCH2 ( 2a), EtOCH2 ( 3a), nPrOCH2 ( 4a)) and fac-[99mTc(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-[99mTc(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 invivo yielding fac-[99mTc(CO)3{HO(CH2)2NHCH2CH(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), nPrOCH2( 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 confirmed the presence of facial and tridentate (3-N3) anchor ligands. Solution NMR studies have also shown that this 3-N3 coordination mode is retained in solution for all complexes ( 2–7).

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