公开(公告)号：US11420910B2

公开(公告)日：2022-08-23

申请号：US15522859

申请日：2015-10-29

申请人： KATHOLIEKE UNIVERSITEIT LEUVEN

发明人： Ahamed Muneer Syed Musthakahmed ,  Emilie Billaud ,  Guy Bormans ,  Frederik Cleeren ,  Joan Lecina ,  Alfons Verbruggen

IPC分类号： A61K51/00 ,  A61M36/14 ,  C07B59/00 ,  C07C259/06 ,  C07D243/08 ,  C07C229/14 ,  C07C229/16 ,  C07C229/38 ,  C07C229/42 ,  C07C331/28 ,  C07D255/02 ,  C07D213/38 ,  C07C215/50 ,  A61K51/04 ,  A61K51/08 ,  A61K51/10 ,  C07K1/13 ,  G01N33/534

摘要： New chelators such as H3L1, H3L2, H3L3, H3L26 and derivatives were synthesized for the complexation of {Al18F}2+. These new chelators are able to complex {AI18F}2+ with good radiochemical yields using a labeling temperature of 37° C. The stability of the new Al18F-complexes was tested in phosphate buffered saline (PBS) at pH 7 and in rat serum. AI18F-L3 and AI18F-L26 showed a stability comparable to that of the previously reported Al18F-NODA. Moreover, the biodistribution of Al18F-L3 and AI18F-L26 showed absence of in vivo demetallation since only very limited bone uptake was observed, whereas the major fraction of activity 60 min p.i. was observed in liver and intestine due to hepatobiliary clearance of the radiolabeled ligand. The chelators H3L3 and Al18F-L26 demonstrated to be a good lead candidates for the labeling of heat sensitive biomolecules with 18F-fluorine and derivatives have been synthesized. We have explored the complexation of {AI18F}2+ with new chelators and obtained very favourable radiochemical yields (>85%) using a labeling temperature of 37° C. The stability of the new Al18F-complexes was tested in phosphate buffered saline (PBS) at pH 7 and in rat serum at 37° C., where AI18F-L3 and AI18F-L26 showed a stability comparable to that of the previously reported Al18F-NODA. Moreover, the biodistribution of Al18F-L3 and Al18F-L26 showed high stability, since only very limited bone uptake—which would be an indication of release of fluorine-18 in the form of fluoride—was observed, whereas the major fraction of activity 60 min p.i. was observed in liver and intestines due to hepatobiliary clearance of the radiolabeled ligand. The chelators H3L3 and H3L26 demonstrated to be good lead candidates for the labeling of heat sensitive biomolecules with 18F-fluorine and several derivatives have been synthesized.

公开(公告)号：US20180273441A1

公开(公告)日：2018-09-27

申请号：US15522859

申请日：2015-10-29

申请人： KATHOLIEKE UNIVERSITEIT LEUVEN

发明人： Ahamed Muneer Syed Musthakahmed ,  Emilie Billaud ,  Guy Bormans ,  Frederik Cleeren ,  Joan Lecina ,  Alfons Verbruggen

IPC分类号： C07B59/00 ,  G01N33/534 ,  C07K1/13 ,  A61K51/08 ,  A61K51/04 ,  A61K51/10 ,  C07C229/14 ,  C07C229/16 ,  C07C229/38 ,  C07C229/42 ,  C07C259/06 ,  C07C331/28 ,  C07D213/38 ,  C07D243/08 ,  C07D255/02

CPC分类号： C07B59/008 ,  A61K51/0482 ,  A61K51/088 ,  A61K51/1093 ,  A61K2123/00 ,  C07B2200/05 ,  C07B2200/07 ,  C07C215/50 ,  C07C229/14 ,  C07C229/16 ,  C07C229/38 ,  C07C229/42 ,  C07C259/06 ,  C07C331/28 ,  C07C2601/08 ,  C07C2601/14 ,  C07D213/38 ,  C07D243/08 ,  C07D255/02 ,  C07K1/13 ,  G01N33/534

摘要： New chelators such as H3L1, H3L2, H3L3, H3L26 and derivatives were synthesized for the complexation of {Al18F}2+. These new chelators are able to complex {AI18F}2+ with good radiochemical yields using a labeling temperature of 37° C. The stability of the new Al18F-complexes was tested in phosphate buffered saline (PBS) at pH 7 and in rat serum. AI18F-L3 and AI18F-L26 showed a stability comparable to that of the previously reported Al18F-NODA. Moreover, the biodistribution of Al18F-L3 and Al18F-L26 showed absence of in vivo demetallation since only very limited bone uptake was observed, whereas the major fraction of activity 60 min p.i. was observed in liver and intestine due to hepatobiliary clearance of the radiolabeled ligand. The chelators H3L3 and Al18F-L26 demonstrated to be a good lead candidates for the labeling of heat sensitive biomolecules with 18F-fluorine and derivatives have been synthesized. We have explored the complexation of {AI18F}2+ with new chelators and obtained very favourable radiochemical yields (>85%) using a labeling temperature of 37° C. The stability of the new Al18F-complexes was tested in phosphate buffered saline (PBS) at pH 7 and in rat serum at 37° C., where AI18F-L3 and AI18F-L26 showed a stability comparable to that of the previously reported Al18F-NODA. Moreover, the biodistribution of Al18F-L3 and Al18F-L26 showed high stability, since only very limited bone uptake—which would be an indication of release of fluorine-18 in the form of fluoride—was observed, whereas the major fraction of activity 60 min p.i. was observed in liver and intestines due to hepatobiliary clearance of the radiolabeled ligand. The chelators H3L3 and H3L26 demonstrated to be good lead candidates for the labeling of heat sensitive biomolecules with 18F-fluorine and several derivatives have been synthesized.