Open AccessDevelopment of Novel 18F-PET Agents for Tumor Hypoxia Imaging
Author(s) -
Li Wang,
Hui Wang,
Kun Shen,
Hyejin Park,
Tao Zhang,
Xuedan Wu,
Mei Hu,
Hong Yuan,
Yue Chen,
Zhanhong Wu,
Qiu Wang,
Zibo Li
Publication year - 2021
Publication title -
journal of medicinal chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.01
H-Index - 261
eISSN - 1520-4804
pISSN - 0022-2623
DOI - 10.1021/acs.jmedchem.0c01962
Subject(s) - tumor hypoxia , chemistry , in vivo , positron emission tomography , hypoxia (environmental) , ex vivo , linker , imaging agent , sulfonyl , metastasis , cancer research , nuclear medicine , radiation therapy , in vitro , biochemistry , medicine , cancer , oxygen , biology , alkyl , microbiology and biotechnology , organic chemistry , computer science , operating system
Tumor hypoxia is a major factor responsible for tumor progression, metastasis, invasion, and treatment resistance, leading to low local tumor control and recurrence after radiotherapy in cancers. Here, 18 F-positron emission tomography (PET) probes are developed for visualizing viable hypoxic cells in biopsies. Pimonidazole derivatives and nitroimidazole-based agents bearing sulfonyl linkers were evaluated. A small-animal PET study showed that the tumor uptake of [ 18 F]- 23 [poly(ethylene glycols) (PEG)-sulfonyl linker] of 3.36 ± 0.29%ID/g was significantly higher ( P < 0.01) than that of [ 18 F]- 20 (piperazine-linker tracer, 2.55 ± 0.49%ID/g) at 2 h postinjection in UPPL tumors. The tumor-to-muscle uptake ratio of [ 18 F]- 23 (2.46 ± 0.48 at 2 h pi) was well improved compared with that of [ 18 F]-FMISO (1.25 ± 0.14 at 2 h pi). A comparable distribution pattern was observed between ex vivo autoradiography of [ 18 F]- 23 and pimonidazole staining of the neighboring slice, indicating that [ 18 F]- 23 is a promising PET agent for hypoxia imaging.