http://www.cnr.it/ontology/cnr/individuo/prodotto/ID317954
[Tc-99m(N)PNP]-scaffold for SPECT of multidrug resistance: Early in-vitro study (Abstract in rivista)
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- Label
- [Tc-99m(N)PNP]-scaffold for SPECT of multidrug resistance: Early in-vitro study (Abstract in rivista) (literal)
- Anno
- 2014-01-01T00:00:00+01:00 (literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
- 10.1016/j.nucmedbio.2014.05.033 (literal)
- Alternative label
Bolzati, C.; Gandin, V.; Morellato, N.; Salvarese, N.; Marzano, C.; Carpanese, D.; Melendez-Alafort, L.; Rosato, A. (2014)
[Tc-99m(N)PNP]-scaffold for SPECT of multidrug resistance: Early in-vitro study
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- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
- Bolzati, C.; Gandin, V.; Morellato, N.; Salvarese, N.; Marzano, C.; Carpanese, D.; Melendez-Alafort, L.; Rosato, A. (literal)
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- 1, 4 Consiglio Nazionale delle Ricerche (CNR);
2-7 University of Padua; University of Padua (literal)
- Titolo
- [Tc-99m(N)PNP]-scaffold for SPECT of multidrug resistance: Early in-vitro study (literal)
- Abstract
- 99mTc(N)-DBODC(PNP5) [DBODC = bis(N-ethoxyethyl)dithiocarbamato; PNP5 = bis(dimethoxypropylphosphinoethyl)ethoxyethylamine] is a cationic mixed-compound, originally investigated as myocardial imaging agent, identified as suitable scaffold to devise 99mTc-agents for SPECT of multidrug resistance (MDR).
To evaluate the impact of the [99mTc(N)PNP]-moiety on the tumor cell accumulation and on MDR recognition, different 99mTc(N)-DBODC(PNP5) like complexes were synthesized varying the substituents on the PNP ligand [PNPn = PNP3 bis(dimethoxypropylphosphinoethyl)-methoxyethylamine; PNP7 (bis(dimethoxyethylphosphinoethyl)-ethoxyethylamine); PNP10 (bis(dimethoxyethylphosphinoethyl)-methoxyethylamine)]. The 99mTc(N)-DBODC(PNPn) uptake was evaluated in human cancer cell lines (MCF7 and MCF7/ADR), and in the corresponding sub-lines using 99mTc-sestamibi and 99mTc(N)-DBODC(PNP5) as references.
A significant increase of %cell-uptake of 99mTc(N)-DBODC(PNP7) and 99mTc(N)-DBODC(PNP10) was observed in drug-sensitive cell lines with respect to 99mTc-sestamibi and 99mTc(N)DBODC(PNP5). This amount was two and three times the %cell-uptake of the reference compounds. A reduction of the net cell uptake between drug-sensitive and drug-resistant cell lines was detected (p < 0.001).
Changing chemical-physical properties of [99mTc(N)PNP]-moiety significantly affects the capability of the complexes to cross the plasma membrane increasing their %cell-uptake and affinity for MDR transporters. 99mTc(N)-DBODC(PNP7) and 99mTc(N)-DBODC(PNP10) are good candidates for in-vivo exploration of MDR.
This research was supported by MIUR (PRIN 20097FJHPZ-004) and by AIRC (IG-13121). (literal)
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