Novel [99mTcIII(PS)2(Ln)] Mixed-Ligand Compounds (PS = Phosphino-thiolate; L = Dithiocarbamate) Useful in Design and Development of TcIII-Based Agents: Synt
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- 作者：Nicola Salvarese ; Nicol貌 Morellato ; Antonio Rosato ; Laura Mel茅ndez-Alafort ; Fiorenzo Refosco ; Cristina Bolzati
- 刊名：Journal of Medicinal Chemistry
- 出版年：2014
- 出版时间：November 13, 2014
- 年：2014
- 卷：57
- 期：21
- 页码：8960-8970
- 全文大小：383K
- ISSN：1520-4804
文摘
A general procedure for the preparation of a new class of neutral six-coordinated mixed ligand [99mTcIII(PS)2(Ln)] compounds (PS = trisalkyl-phosphino-thiolate; Ln = dithiocarbamate) is reported as well as their in vitro stability and the ex vivo tissue distribution studies. [99mTc(PS)2(Ln)] complexes were prepared in high yield in nearly physiologic conditions following a one-pot procedure. For instance, the chemical identity of [99mTc(PSiso)2(L1)] (PSiso = 2-(diisopropylphosphino)ethanethiol; L1 = pyrrolidine dithiocarbamate) was determined by HPLC comparison with the corresponding 99gTc-complex. All complexes comprise the stable [99mTcIII(PS)2]+ moiety, where the remaining two coordination positions are saturated by a dithiocarbamate chelate, also carrying bioactive molecules (e.g., 2-methoxyphenylpiperazine). [99mTc(PS)2(Ln)] complexes were inert toward ligand exchange reactions. No significant in vitro and in vivo biotransformation were observed, underlining their remarkable thermodynamic stability and kinetic inertness. These results could be conveniently utilized to devise a novel class of 99mTcIII-based compounds useful in radiopharmaceutical applications.