Insights into the failure of the potential, neutral myocardial imaging agent TcN-NOET: physicochemical identification of by-products and degradation species (Articolo in rivista)

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  • Insights into the failure of the potential, neutral myocardial imaging agent TcN-NOET: physicochemical identification of by-products and degradation species (Articolo in rivista) (literal)
Anno
  • 2012-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1016/j.nucmedbio.2011.09.007 (literal)
Alternative label
  • Tisato F.; Bolzati C.; Refosco F.; Porchia M.; Seraglia R.; Carta D.; Pasqualini R. (2012)
    Insights into the failure of the potential, neutral myocardial imaging agent TcN-NOET: physicochemical identification of by-products and degradation species
    in Nuclear medicine and biology
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Tisato F.; Bolzati C.; Refosco F.; Porchia M.; Seraglia R.; Carta D.; Pasqualini R. (literal)
Pagina inizio
  • 335 (literal)
Pagina fine
  • 346 (literal)
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  • http://www.sciencedirect.com/science/article/pii/S0969805111002289 (literal)
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  • 39 (literal)
Rivista
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  • Nuclear Medicine and Biology xx (2011) xxx–xxx Available online at www.sciencedirect.com (literal)
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  • 3 (literal)
Note
  • Scopu (literal)
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • 1,2,3,4 : - ICIS-CNR, Corso Stati Uniti, 4, 35127 Padova, Italy / 2,6 : - Department Pharmaceutical Sciences, University of Padova, Via Marzolo, 5, 35131 Padova, Italy / 5 : - ISTM-CNR, Corso Stati Uniti, 4, 35131 Padova, Italy / 7 : - IBA Centre de Saclay, B.P. 32, 91192 Gif-sur-Yvette, France (literal)
Titolo
  • Insights into the failure of the potential, neutral myocardial imaging agent TcN-NOET: physicochemical identification of by-products and degradation species (literal)
Abstract
  • Introduction: The neutral complex [Tc-99m(N)(NOEt)(2)], often referred to as TcN-NOET [NOEt=N-ethoxy,N-ethyldithiocarbamate(1-)], was proposed several years ago as a myocardial imaging agent. Despite some favorable clinical properties evidenced during phase I and phase II studies, the overall results of the European and American phase III clinical studies have been judged insufficient for a successful approval process by the regulatory agencies. Methods: Non-carrier-added and carrier-added experiments using short-lived Tc-99m and long-lived Tc-99g have been utilized to prepare a series of bis-substituted [Tc(N)(DTC)(2)] complexes [DTC=dithiocarbamate(1-)]. They have been purified by means of chromatographic techniques (high-performance liquid chromatography and thin-layer chromatography) and identified via double detection (UV-vis and radiometry) by comparison with authenticated samples of Tc-99g compounds prepared by conventional coordination chemistry procedures. Results: The molecular structure of the lipophilic, neutral complex cis-[Tc(N)(NOEt)(2)] has been assigned by comparison with similar nitrido-Tc(V) complexes already reported in the literature. Novel bis-substituted nitrido-Tc complexes containing hydrolyzed portions of coordinated NOEt, namely, N-ethyldithiocarbamate [NHEt(1-)] and N-hydroxy, N-ethyldithiocarbamate [NOHEt(1-)], have been prepared and characterized by means of multinuclear nuclear magnetic resonance spectroscopy and mass spectrometry. Conclusions: Despite the identification of these \"hydrolyzed\" species, it is still unclear whether the failure to reach the clinical goal of the perfusion tracer [Tc-99m(N)(NOEt)(2)] is related to the degradation processes evidenced in this study or is the result of the mediocre imaging properties of the tracer. (literal)
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