[99mTc][Tc(N)(DASD)(PNP n)]+ (DASD = 1,4-Dioxa-8-azaspiro[4,5]decandithiocarbamate, PNP n = Bisphosphinoamine) for Myocardial Imaging: Synthesis, Pharmacological and Pharmacokinetic Studies

Nicola Salvarese, Davide Carta, Cristina Marzano, Gabriele Gerardi, Laura Melendez-Alafort, Cristina Bolzati

Research output: Contribution to journalArticle

Abstract

[99mTc][TcN-DBODC(5) is the lead candidate of a class of cationic complexes proposed as myocardial imaging agents (MPIAs). Phase I clinical studies showed that its clinical properties were comparable to those of the commercially available agents. Thus, modification of [99mTc]TcN-DBODC(5), directed to obtain an ideal myocardial imaging without interference from the adjacent organ activities, is desirable. This work describes the pharmacological and pharmacokinetic development of four new complexes of general formula [99mTc][Tc(N)(DASD)(PNPn)]+, [99mTc]TcN-DASD(n) (DASD = 1,4-dioxa-8-azaspiro[4,5]decandithiocarbamate; PNPn = bisphosphinoamine), proposed as improved MPIAs. Among the tested compounds, [99mTc]TcN-DASD(5) and [99mTc]TcN-DASD(7) showed enhanced heart uptake compared with the gold standards, with a rapid liver washout and superior heart-to-liver ratio. These features might shorten the duration of imaging procedures below 30 min, consenting the early acquisition of high-quality images. In addition, mechanistic studies were performed in cellulo by using human drug-sensitive and drug-resistant cancer cell lines, obtaining results which might be conveniently applied to tumor imaging.

Original languageEnglish
Pages (from-to)11114-11126
Number of pages13
JournalJournal of Medicinal Chemistry
Volume61
Issue number24
DOIs
Publication statusPublished - Dec 27 2018

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Neoplasms
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  • Molecular Medicine
  • Drug Discovery

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[99mTc][Tc(N)(DASD)(PNP n)]+ (DASD = 1,4-Dioxa-8-azaspiro[4,5]decandithiocarbamate, PNP n = Bisphosphinoamine) for Myocardial Imaging : Synthesis, Pharmacological and Pharmacokinetic Studies. / Salvarese, Nicola; Carta, Davide; Marzano, Cristina; Gerardi, Gabriele; Melendez-Alafort, Laura; Bolzati, Cristina.

In: Journal of Medicinal Chemistry, Vol. 61, No. 24, 27.12.2018, p. 11114-11126.

Research output: Contribution to journalArticle

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