| Autor: |
Joaqui-Joaqui MA; Department of Chemistry, University of Minnesota, Minneapolis, Minnesota 55455, United States., Pandey MK; Department of Radiology, Mayo Clinic, Rochester, Minnesota 55905, United States., Bansal A; Department of Radiology, Mayo Clinic, Rochester, Minnesota 55905, United States., Raju MVR; Department of Chemistry, University of Minnesota, Minneapolis, Minnesota 55455, United States., Armstrong-Pavlik F; Department of Chemistry, University of Minnesota, Minneapolis, Minnesota 55455, United States., Dundar A; Department of Radiology, Mayo Clinic, Rochester, Minnesota 55905, United States., Wong HL; Department of Medicinal Chemistry and Institute for Therapeutics Discovery & Development, University of Minnesota, Minneapolis, Minnesota 55414, United States., DeGrado TR; Department of Radiology, Mayo Clinic, Rochester, Minnesota 55905, United States., Pierre VC; Department of Chemistry, University of Minnesota, Minneapolis, Minnesota 55455, United States. |
| Abstrakt: |
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 Ga III 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 Ga III -TREN-CAM. In vivo imaging studies and ex vivo pharmacokinetic and biodistribution studies indicate that the parent [ 68 Ga]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. |
