Biomedical Research Imaging Center, Department of Radiology, and UNC Lineberger Comprehensive Cancer Center, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina 27514, United States.
Department of Nuclear Medicine, Affiliated Hospital of Southwest Medical University, Luzhou 646000, China.
J Med Chem. 2021 May 13;64(9):5593-5602. doi: 10.1021/acs.jmedchem.0c01962. Epub 2021 Apr 26.
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,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 [F]- [poly(ethylene glycols) (PEG)-sulfonyl linker] of 3.36 ± 0.29%ID/g was significantly higher ( < 0.01) than that of [F]- (piperazine-linker tracer, 2.55 ± 0.49%ID/g) at 2 h postinjection in UPPL tumors. The tumor-to-muscle uptake ratio of [F]- (2.46 ± 0.48 at 2 h pi) was well improved compared with that of [F]-FMISO (1.25 ± 0.14 at 2 h pi). A comparable distribution pattern was observed between autoradiography of [F]- and pimonidazole staining of the neighboring slice, indicating that [F]- is a promising PET agent for hypoxia imaging.
肿瘤缺氧是导致肿瘤进展、转移、侵袭和治疗抵抗的主要因素，导致癌症患者放疗后局部肿瘤控制率低和复发率高。在这里，我们开发了正电子发射断层扫描（PET）探针，用于可视化活检中存活的缺氧细胞。评估了带有磺酰基连接体的脒基嘧啶衍生物和硝基咪唑类药物。小动物 PET 研究表明，在 UPPL 肿瘤中，[F]-[聚（乙二醇）（PEG）-磺酰基连接体]的肿瘤摄取率（2 h 时为 3.36 ± 0.29%ID/g）明显高于[F]-（哌嗪连接体示踪剂，2.55 ± 0.49%ID/g）（<0.01）。与[F]-FMISO（2 h pi 时为 1.25 ± 0.14）相比，[F]-（2 h pi 时为 2.46 ± 0.48）的肿瘤与肌肉摄取比得到了很好的改善。[F]-与相邻切片中脒基嘧啶染色的放射性自显影观察到相似的分布模式，表明[F]-是一种有前途的缺氧成像 PET 探针。
