TY - JOUR
T1 - Modifying LnHPDO3A Chelates for Improved T 1 and CEST MRI Applications
AU - Ferrauto, Giuseppe
AU - Delli Castelli, Daniela
AU - Leone, Loredana
AU - Botta, Mauro
AU - Aime, Silvio
AU - Baranyai, Zsolt
AU - Tei, Lorenzo
N1 - Publisher Copyright:
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2019/3/15
Y1 - 2019/3/15
N2 - The new ligand HPDO3MA [(R,R,R,R)-10-(2-hydroxypropyl)-α,α′,α′′-trimethyl-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid] was designed to combine and optimize the chemical properties of the macrocyclic ligands HPDO3A and DOTMA. The presence of the methyl groups on the acetic pendant arms of HPDO3A is expected to rigidify the structure of the ligand and favor an increase of the kinetic inertness of the Ln complexes. 1 H NMR spectra of Eu(HPDO3MA) displayed the presence of two pairs of diastereoisomers: SAP (square antiprismatic) and TSAP (twisted square antiprismatic) isomers (56 and 44 %, respectively). In addition, 1 H and 17 O relaxometric NMR studies of Gd(HPDO3MA) showed approximately a 10 % increase in relaxivity and a faster water exchange rate with respect to Gd(HPDO3A). Moreover, a detailed chemical exchange saturation transfer (CEST) characterization of Yb(HPDO3MA) displayed a sensitivity about two times larger than that of Yb(HPDO3A) both in phantom and in cell labeling experiments. Finally, the kinetic inertness of Yb(HPDO3MA) was measured to be twice as high as that of Yb(HPDO3A), with a dissociation half-life at physiological pH of about 2500 years.
AB - The new ligand HPDO3MA [(R,R,R,R)-10-(2-hydroxypropyl)-α,α′,α′′-trimethyl-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid] was designed to combine and optimize the chemical properties of the macrocyclic ligands HPDO3A and DOTMA. The presence of the methyl groups on the acetic pendant arms of HPDO3A is expected to rigidify the structure of the ligand and favor an increase of the kinetic inertness of the Ln complexes. 1 H NMR spectra of Eu(HPDO3MA) displayed the presence of two pairs of diastereoisomers: SAP (square antiprismatic) and TSAP (twisted square antiprismatic) isomers (56 and 44 %, respectively). In addition, 1 H and 17 O relaxometric NMR studies of Gd(HPDO3MA) showed approximately a 10 % increase in relaxivity and a faster water exchange rate with respect to Gd(HPDO3A). Moreover, a detailed chemical exchange saturation transfer (CEST) characterization of Yb(HPDO3MA) displayed a sensitivity about two times larger than that of Yb(HPDO3A) both in phantom and in cell labeling experiments. Finally, the kinetic inertness of Yb(HPDO3MA) was measured to be twice as high as that of Yb(HPDO3A), with a dissociation half-life at physiological pH of about 2500 years.
KW - cell labeling
KW - kinetic inertness
KW - lanthanides
KW - macrocycles
KW - relaxometry
UR - http://www.scopus.com/inward/record.url?scp=85061908762&partnerID=8YFLogxK
U2 - 10.1002/chem.201806023
DO - 10.1002/chem.201806023
M3 - Article
SN - 0947-6539
VL - 25
SP - 4184
EP - 4193
JO - Chemistry - A European Journal
JF - Chemistry - A European Journal
IS - 16
ER -