TY - JOUR
T1 - Catechol-based functionalizable ligands for gallium-68 positron emission tomography imaging
AU - Joaqui-Joaqui, M. Andrey
AU - Pandey, Mukesh K.
AU - Bansal, Aditya
AU - Raju, Mandapati V.Ramakrishnam
AU - Armstrong-Pavlik, Fiona
AU - Dundar, Ayca
AU - Wong, Henry L.
AU - Degrado, Timothy R.
AU - Pierre, Valérie C.
N1 - Funding Information:
The authors acknowledge support from the Minnesota Partnership for Biotechnology and Genomics (Grant 17.38).
PY - 2020/9/8
Y1 - 2020/9/8
N2 - Four tris-bidentate catecholamide (CAM) ligands were synthesized, characterized, and evaluated as ligands for radiolabeling of gallium-68 for positron emission tomography (PET). Three of those ligands, 2,2-Glu-CAM, 3,3-Glu-CAM, and TREN-bisGlyGlu-CAM, incorporate ligand caps that contain a pendant carboxylic group for further conjugation to targeting moieties. The acyclic ligands all exhibited high (>80%) radiolabeling yields after short reaction times (<10 min) at room temperature, a distinct advantage over macrocyclic analogues that display slower kinetics. The stabilities of the four GaIII complexes are comparable to or higher than those of other acyclic ligands used for gallium-68 PET imaging, such as desferrioxamine, with pGa values ranging from 21 to >24, although the functionalizable ligands are less stable than the parent GaIII-TREN-CAM. In vivo imaging studies and ex vivo pharmacokinetic and biodistribution studies indicate that the parent [68Ga]Ga-TREN-CAM is stable in vivo but is rapidly cleared in <15 min, probably via a renal pathway. The rapid and mild radiolabeling conditions, high radiolabeling yields, and high stability in human serum (>95%) render TREN-bisGlyGlu-CAM a promising candidate for gallium-68 chelation.
AB - Four tris-bidentate catecholamide (CAM) ligands were synthesized, characterized, and evaluated as ligands for radiolabeling of gallium-68 for positron emission tomography (PET). Three of those ligands, 2,2-Glu-CAM, 3,3-Glu-CAM, and TREN-bisGlyGlu-CAM, incorporate ligand caps that contain a pendant carboxylic group for further conjugation to targeting moieties. The acyclic ligands all exhibited high (>80%) radiolabeling yields after short reaction times (<10 min) at room temperature, a distinct advantage over macrocyclic analogues that display slower kinetics. The stabilities of the four GaIII complexes are comparable to or higher than those of other acyclic ligands used for gallium-68 PET imaging, such as desferrioxamine, with pGa values ranging from 21 to >24, although the functionalizable ligands are less stable than the parent GaIII-TREN-CAM. In vivo imaging studies and ex vivo pharmacokinetic and biodistribution studies indicate that the parent [68Ga]Ga-TREN-CAM is stable in vivo but is rapidly cleared in <15 min, probably via a renal pathway. The rapid and mild radiolabeling conditions, high radiolabeling yields, and high stability in human serum (>95%) render TREN-bisGlyGlu-CAM a promising candidate for gallium-68 chelation.
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U2 - 10.1021/acs.inorgchem.0c00975
DO - 10.1021/acs.inorgchem.0c00975
M3 - Article
C2 - 32820888
AN - SCOPUS:85090482798
SN - 0020-1669
VL - 59
SP - 12025
EP - 12038
JO - Inorganic chemistry
JF - Inorganic chemistry
IS - 17
ER -