The patent badge is an abbreviated version of the USPTO patent document. The patent badge does contain a link to the full patent document.
The patent badge is an abbreviated version of the USPTO patent document. The patent badge covers the following: Patent number, Date patent was issued, Date patent was filed, Title of the patent, Applicant, Inventor, Assignee, Attorney firm, Primary examiner, Assistant examiner, CPCs, and Abstract. The patent badge does contain a link to the full patent document (in Adobe Acrobat format, aka pdf). To download or print any patent click here.
Patent No.:
Date of Patent:
Jan. 03, 2023
Filed:
Mar. 15, 2019
Universität Zu Köln, Cologne, DE;
Bernd Neumaier, Cologne, DE;
Boris Zlatopolskiy, Cologne, DE;
Philipp Krapf, Siegburg, DE;
Raphael Richarz, Leverkusen, DE;
Alexander Drzezga, Cologne, DE;
Universität zu Köln, Cologne, DE;
Abstract
6-[F]Fluoro-2-alkoxynicotinoyl substituted Lys-C(O)-Glu derivatives were identified as efficient imaging probes for PSMA expressing tissues in comparison to other known PSMA specific ligands like [F]DCFPyL, [Ga]HBED-CC-PSMA, [F]PSMA-1007 and [AlF]HBED-CC-PSMA. Unexpectedly, the 6-[F]fluoro-2-alkoxy and 6-[F]fluoro-4-alkoxy substituted analogs showed significant differences in accumulation in PSMA expressing prostate tumor cells. Whereas the 2-alkoxy derivative showed cellular uptake values higher than [F]DCFPyL, the cellular uptake of the corresponding 4-alkoxy substituted derivative was significantly lower. Furthermore, in vivo PET studies with 2-alkoxy-substituted probes demonstrated excellent visualization of PSMA positive ganglia with extremely high target to background ratio. In contrast, the 4-alkoxy substituted derivatives showed less favorable biodistribution with significantly lower uptake in PSMA positive tissues. Especially, theF-labeled 2-methoxy derivate ((2S)-2-({[(1S)-1-carboxy-5-[(6-[F]fluoro-2-methoxypyridin-3-yl)formamido]pentyl]carbamoyl}-amino)pentanedioic acid) demonstrated exceptional clinical efficiency in detecting small PCa lesions, including those which could not be visualized with [Ga]HBED-CC-PSMA representing currently the gold standard for the diagnosis of recurrent PCa. Furthermore, this probe is easily accessible on a preparative scale in commercially available automated synthesis modules like GE FASTlab and TRACERlab FX N Pro. Consequently, the novel probe is a valuable tool for the visualization of ganglia and reendothelialization as well as for the diagnosis of glioma, neuropathic pain and atherosclerotic plaques.