Biomolecules | |
A Series of PSMA-Targeted Near-Infrared Fluorescent Imaging Agents | |
Il Minn1  Ronnie C. Mease1  Martin G. Pomper1  Samit Chatterjee1  Alla Lisok1  Ying Chen1  Steven P. Rowe1  Mary Brummet1  Sangeeta Ray Banerjee1  | |
[1] The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; | |
关键词: NIRF; molecular imaging; fluorescence-guided surgery; prostate-specific membrane antigen; DyLight800; | |
DOI : 10.3390/biom12030405 | |
来源: DOAJ |
【 摘 要 】
We have synthesized a series of 10 new, PSMA-targeted, near-infrared imaging agents intended for use in vivo for fluorescence-guided surgery (FGS). Compounds were synthesized from the commercially available amine-reactive active NHS ester of DyLight800. We altered the linker between the PSMA-targeting urea moiety and the fluorophore with a view to improve the pharmacokinetics. Chemical yields for the conjugates ranged from 51% to 86%. The Ki values ranged from 0.10 to 2.19 nM. Inclusion of an N-bromobenzyl substituent at the ε-amino group of lysine enhanced PSMA+ PIP tumor uptake, as did hydrophilic substituents within the linker. The presence of a polyethylene glycol chain within the linker markedly decreased renal uptake. In particular, DyLight800-10 demonstrated high specific uptake relative to background signal within kidney, confirmed by immunohistochemistry. These compounds may be useful for FGS in prostate, renal or other PSMA-expressing cancers.
【 授权许可】
Unknown