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Novel multifunctional 18 F-labelled PET tracer with prostate-specific membrane antigen-targeting and hypoxia-sensitive moieties

Authors
 Young-Do Kwon  ;  Jun Young Lee  ;  Minh Thanh La  ;  Sun Joo Lee  ;  Sun-Hwa Lee  ;  Jeong Hoon Park  ;  Hee-Kwon Kim 
Citation
 EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, Vol.189 : 112099, 2020-03 
Journal Title
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
ISSN
 0223-5234 
Issue Date
2020-03
MeSH
Animals ; Antigens, Surface / metabolism ; Apoptosis ; Cell Proliferation ; Fluorine Radioisotopes / chemistry ; Fluorine Radioisotopes / pharmacokinetics* ; Glutamate Carboxypeptidase II / antagonists & inhibitors* ; Glutamate Carboxypeptidase II / metabolism ; Humans ; Hypoxia* ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Models, Molecular ; Positron-Emission Tomography / methods* ; Prostatic Neoplasms / diagnostic imaging ; Prostatic Neoplasms / metabolism ; Prostatic Neoplasms / pathology* ; Radiopharmaceuticals / chemistry ; Radiopharmaceuticals / pharmacokinetics* ; Tissue Distribution ; Tumor Cells, Cultured ; Xenograft Model Antitumor Assays
Keywords
Prostate cancer ; Prostate-specific membrane antigen ; Fluorine-18 ; Positron-emission tomography ; Cupper-free click reaction
Abstract
Prostate cancer is one of the most frequently found cancers in men worldwide. Prostate-specific membrane antigen (PSMA) is typically highly expressed in prostate cancer, and the Glu-Urea-Lys (GUL) structure has recently received considerable attention as a key unit of PSMA-targeting agents. Additionally, one of the common characteristics of many solid tumors, such as prostate cancer, is hypoxia. In this study, novel multifunctional PSMA inhibitors containing a PSMA-targeting moiety either with or without a hypoxia-sensitive moiety (F-18-PEG(3)-ADIBOT-2NI-GUL and F-18-PEGS-ADIBOT-GUL, respectively; ADIBOT: azadibenzocyclooctatriazole, 2N1: 2-nitroimidazole) were designed and synthesized, and their feasibility as PET tracers for prostate cancer imaging studies was examined. The compounds labelled with F-18 via the copper-free click reaction were stable in human serum and showed nanomolar binding affinities in in vitro PSMA binding assays. Micro-PET and biodistribution studies indicate that both F-18-labelled inhibitors successfully accumulated in prostate cancer regions, and F-18-PEGS-ADIBOT-2NI-GUL showed a 2-fold higher tumor-to-total non-target organ ratio than that of F-18-PEGS-ADIBOT-GUL, suggesting that the synergistic effects of the PSMA-targeting GUL moiety and the hypoxia-sensitive 2-nitroimidazole moiety can increase tumor uptake of the novel PET tracers in prostate cancer. These findings suggest that this novel multifunctional PET tracer with an F-18-labelled PSMA inhibitor and a 2-nitroimidazole moiety is a potent candidate to provide better diagnosis of prostate cancer via PET imaging studies. (C) 2020 Elsevier Masson SAS. All rights reserved.
Full Text
https://www.sciencedirect.com/science/article/pii/S0223523420300660
DOI
10.1016/j.ejmech.2020.112099
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Nuclear Medicine (핵의학교실) > 1. Journal Papers
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/190202
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