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001-es BibID:	BIBFORM038094
Első szerző:	Rojas-Quijano, Federico A.
Cím:	Synthesis and Characterization of a Hypoxia-Sensitive MRI Probe / Federico A. Rojas-Quijano, Gyula Tircsó, Enikő Tircsóné Benyó, Zsolt Baranyai, Huan Tran Hoang, Ferenc K. Kálmán, Praveen K. Gulaka, Vikram D. Kodibagkar, Silvio Aime, Zoltán Kovács, A. Dean Sherry
Dátum:	2012
ISSN:	0947-6539
Megjegyzések:	Tissue hypoxia occurs in pathologic conditions, such as cancer, ischemic heart disease and stroke when oxygen demand is greater than oxygen supply. An imaging method that can differentiate hypoxic versus normoxic tissue could have an immediate impact on therapy choices. In this work, the gadolinium complex of 1,4,7,10-tetraaza-1,4,7,10-tetraacetate (DOTA) with a 2-nitroimidazole attached to one carboxyl group via an amide linkage was prepared, characterized and tested as a hypoxia-sensitive MRI agent. A control complex, Gd(DO3A-monobutylamide), was also prepared in order to test whether the nitroimidazole sidechain alters either the water proton T1 relaxivity or the thermodynamic stability of the complex. The stabilities of these complexes were lower than thatof Gd(DOTA)- as expected for monoamide derivatives. The water proton T1 relaxivity (r1), bound water residence lifetime (tM) and rotational correlation time (tR) of both complexes was determined by relaxivity measurements, variable temperature 17O NMR spectroscopy and proton nuclear magnetic relaxation dispersion (NMRD) studies. The resulting parameters (r1=6.38 mM-1 s-1 at 20 MHz, tM=0.71 ms, tR=141 ps) determined for the nitroimidazole derivative closely parallel those of other Gd(DO3A-monoamide) complexes of similar molecular size. In vitro MR imaging experiments with 9L rat glioma cells maintained under nitrogen (hypoxic) versus oxygen (normoxic) gas showed that both agents enter cells but only the nitroimidazole derivative was trapped in cells maintained under N2 as evidenced by an approximately twofold decrease in T1 measured for hypoxic cells versus normoxic cells exposed to this agent. These results suggest that the nitroimidazole derivative might serve as a molecular reporter for discriminating hypoxic versus normoxic tissues by MRI.
Tárgyszavak:	Természettudományok Kémiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban Molekulatudomány
Megjelenés:	Chemistry-A European Journal. - 18 : 31 (2012), p. 9669-9676. -
További szerzők:	Tircsó Gyula (1977-) (vegyész, kémia tanár) Tircsóné Benyó Enikő (1977-) (vegyész, kémia tanár) Baranyai Zsolt (1977-) (vegyész) Tran-Hoang, Huan Kálmán Ferenc K. (1978-) (vegyész) Gulaka, Praveen K. Kodibagkar, Vikram D. Aime, Silvio Kovács Zoltán (1963-) (vegyész, angol szakfordító) Sherry, A. Dean
Pályázati támogatás:	TÁMOP-4.2.1/B-09/1/KONV-2010-0007 TÁMOP Bimodális kontrasztanyagok tervezése, előállítása és komplexeik fizikai-kémiai tulajdonságaik jellemzése TÁMOP-4.2.2./B-10/1-2010-0024 TÁMOP K84291 OTKA PD83253 OTKA
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