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001-es BibID:	BIBFORM107388
035-os BibID:	(Wos)000674274600001 (Scopus)85112868977
Első szerző:	Horváth Dávid (vegyész)
Cím:	Towards 213 Bi alpha-therapeutics and beyond: unravelling the foundations of efficient Bi III complexation by DOTP / Dávid Horváth, Fabio Travagin, Nicol Guidolin, Federica Buonsanti, Gyula Tircsó, Imre Tóth, Frank Bruchertseifer, Alfred Morgenstern, Johannes Notni, Giovanni B. Giovenzana, Zsolt Baranyai
Dátum:	2021
ISSN:	2052-1553
Megjegyzések:	Bismuth isotopes are attracting increasing attention for their potential applications in diagnostics and therapy. The emerging use of 213Bi in targeted alpha-therapy (TAT) is a particularly relevant example because it is available from radionuclide generators. A fast formation of stable BiIII-complexes is important for the safe and efficient preparation of labelled (bio)conjugates. Macrocyclic chelating agents are currently the best choice in terms of stability of the corresponding BiIII-complexes. In this work, a thorough study of the thermodynamics and kinetics of formation of BiIII-DOTP including radio-labelling and the comparison with the congener BiIII-DOTA is undertaken. The BiIII-DOTP complex is characterised by a fast formation kinetics (kBi(H2DOTP) = 0.33 s-1), an outstanding thermodynamic stability (log KBiDOTP = 38.67) and an impressive kinetic inertness (t1/2pH=3 = 47 600 h). The results clearly demonstrate that DOTP is a better chelating agent for BiIII both in terms of thermodynamic stability and in terms of kinetics of formation, with clear advantages in the radiolabelling of short-lived bismuth isotopes.
Tárgyszavak:	Természettudományok Kémiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk
Megjelenés:	Inorganic Chemistry Frontiers. - 8 : 16 (2021), p. 3893-3904. -
További szerzők:	Travagin, Fabio Guidolin, Nicol Buonsanti, Federica Tircsó Gyula (1977-) (vegyész, kémia tanár) Tóth Imre (1950-) (vegyész) Bruchertseifer, Frank Morgenstern, Alfred Notni, Johannes Giovenzana, Giovanni Battista Baranyai Zsolt (1977-) (vegyész)
Pályázati támogatás:	K-128201 OTKA K-120224 OTKA K-134694 OTKA GINOP-2.3.2-15-2016-00008 GINOP
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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001-es BibID:	BIBFORM076233
Első szerző:	Wurzer, Alexander
Cím:	Synthesis of Symmetrical Tetrameric Conjugates of the Radiolanthanide Chelator DOTPI for Application in Endoradiotherapy by Means of Click Chemistry / Alexander Wurzer, Adrienn Vágner, Dávid Horváth, Flóra Fellegi, Hans-Jürgen Wester, Ferenc K. Kálmán, Johannes Notni
Dátum:	2018
ISSN:	2296-2646
Megjegyzések:	Due to its 4 carbonic acid groups being available for bioconjugation, the cyclen tetraphosphinate chelator DOTPI, 1,4,7,10-tetraazacyclododecane-1,4,7, 10-tetrakis[methylene(2-carboxyethylphosphinic acid)], represents an ideal scaffold for synthesis of tetrameric bioconjugates for labeling with radiolanthanides, to be applied as endoradiotherapeuticals. We optimized a protocol for bio-orthogonal DOTPI conjugation via Cu(I)-catalyzed Huisgen-cycloaddition of terminal azides and alkynes (CuAAC), based on the building block DOTPI(azide)4. A detailed investigation of kinetic properties of Cu(II)-DOTPI complexes aimed at optimization of removal of DOTPI-bound copper by transchelation. Protonation and equilibrium properties of Ca(II)-, Zn(II), and Cu(II)-complexes of DOTPI and its tetra-cyclohexylamide DOTPI(Chx)4 (a model for DOTPI conjugates) as well as kinetic inertness (transchelation challenge in the presence of 20 to 40-fold excess of EDTA) were investigated by pH-potentiometry and spectrophotometry. Similar stability constants of CaII-, ZnII, and CuII-complexes of DOTPI (logK(CaL) = 8.65, logK(ZnL = 15.40, logK(CuL) = 20.30) and DOTPI(Chx)4 (logK(CaL) = 8.99, logK(ZnL) = 15.13, logK(CuL) = 20.42) were found. Transchelation of Cu(II)-complexes occurs via proton-assisted dissociation, whereafter released Cu(II) is scavenged by EDTA. The corresponding dissociation rates [kd = 25 ? 10?7 and 5 ? 10?7 s?1 for Cu(DOTPI) and Cu(DOTPI(Chx)4), respectively, at pH 4 and 298 K] indicate that conjugation increases the kinetic inertness by a factor of 5. However, demetallation is completed within 4.5 and 7.2 h at pH 2 and 25?C, respectively, indicating that Cu(II) removal after formation of CuAAC can be achieved in an uncomplicated manner by addition of excess H4EDTA. For proof-of-principle, tetrameric DOTPI conjugates of the prostate-specific membrane antigen (PSMA) targeting motif Lys-urea-Glu (KuE) were synthesized via CuAAC as well as dibenzo-azacyclooctine (DBCO) based, strain-promoted click chemistry (SPAAC), which were labeled with Lu-177 and subsequently evaluated in vitro and in SCID mice bearing subcutaneous LNCaP tumor (PSMA+ human prostate carcinoma) xenografts. High affinities (3.4 and 1.4 nM, respectively) and persistent tumor uptakes (approx. 3.5% 24 h after injection) confirm suitability of DOTPI-based tetramers for application in targeted radionuclide therapy.
Tárgyszavak:	Természettudományok Kémiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:	Frontiers in Chemistry. - 6 (2018), p. 1-11. -
További szerzők:	Vágner Adrienn (1990-) (vegyész, kémikus) Horváth Dávid (1991-) (vegyész) Fellegi Flóra Wester, Hans J. Kálmán Ferenc K. (1978-) (vegyész) Notni, Johannes
Pályázati támogatás:	GINOP-2.3.2-15-2016-00008 GINOP GINOP-2.3.3-15-2016-00004 GINOP Bolyai János Kutatási Ösztöndíj Egyéb
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