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 language | English |
|---|---|
| Pages (from-to) | 11114-11126 |
| Number of pages | 13 |
| Journal | Journal of Medicinal Chemistry |
| Volume | 61 |
| Issue number | 24 |
| DOIs | |
| Publication status | Published - Dec 27 2018 |
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ASJC Scopus subject areas
- Molecular Medicine
- Drug Discovery
Cite this
[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 journal › Article
}
TY - JOUR
T1 - [99mTc][Tc(N)(DASD)(PNP n)]+ (DASD = 1,4-Dioxa-8-azaspiro[4,5]decandithiocarbamate, PNP n = Bisphosphinoamine) for Myocardial Imaging
T2 - Synthesis, Pharmacological and Pharmacokinetic Studies
AU - Salvarese, Nicola
AU - Carta, Davide
AU - Marzano, Cristina
AU - Gerardi, Gabriele
AU - Melendez-Alafort, Laura
AU - Bolzati, Cristina
PY - 2018/12/27
Y1 - 2018/12/27
N2 - [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.
AB - [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.
UR - http://www.scopus.com/inward/record.url?scp=85058896946&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85058896946&partnerID=8YFLogxK
U2 - 10.1021/acs.jmedchem.8b01191
DO - 10.1021/acs.jmedchem.8b01191
M3 - Article
AN - SCOPUS:85058896946
VL - 61
SP - 11114
EP - 11126
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 24
ER -