Novel [99mTcIII(PS)2(Ln)] mixed-ligand compounds (PS = phosphino-thiolate; L = dithiocarbamate) useful in design and development of TcIII-based agents: Synthesis, in vitro, and ex vivo biodistribution studies

Nicola Salvarese, Nicolò Morellato, Antonio Rosato, Laura Meléndez-Alafort, Fiorenzo Refosco, Cristina Bolzati

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)8960-8970
Number of pages11
JournalJournal of Medicinal Chemistry
Volume57
Issue number21
DOIs
Publication statusPublished - Nov 13 2014

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery
  • Medicine(all)

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