Development of Novel 18F-PET Agents for Tumor Hypoxia Imaging.

Abstract

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,18F-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 [18F]-23 [poly(ethylene glycols) (PEG)-sulfonyl linker] of 3.36 ± 0.29%ID/g was significantly higher (P < 0.01) than that of [18F]-20 (piperazine-linker tracer, 2.55 ± 0.49%ID/g) at 2 h postinjection in UPPL tumors. The tumor-to-muscle uptake ratio of [18F]-23 (2.46 ± 0.48 at 2 h pi) was well improved compared with that of [18F]-FMISO (1.25 ± 0.14 at 2 h pi). A comparable distribution pattern was observed between ex vivo autoradiography of [18F]-23 and pimonidazole staining of the neighboring slice, indicating that [18F]-23 is a promising PET agent for hypoxia imaging.

• Authors: Li Wang, Hui Wang, Kun Shen, Hyejin Park, Tao Zhang, Xuedan Wu, Mei Hu, Hong Yuan, Yue Chen, Zhanhong Wu, Qiu Wang, Zibo Li
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 64 Issue 9 Pg. 5593-5602 (05 13 2021) ISSN: 1520-4804 [Electronic] United States
• PMID: 33901402 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Fluorine Radioisotopes
• Nitroimidazoles
• Radiopharmaceuticals
• Sulfinic Acids
• Polyethylene Glycols
• pimonidazole
• Fluorine-18

Topics

• Animals
• Cell Line, Tumor
• Fluorine Radioisotopes (chemistry)
• Humans
• Mice
• Mice, Inbred C57BL
• Mice, Nude
• Neoplasms (diagnostic imaging)
• Nitroimidazoles (chemistry)
• Polyethylene Glycols (chemistry)
• Positron-Emission Tomography
• Radiopharmaceuticals (chemical synthesis, chemistry, metabolism)
• Sulfinic Acids (chemistry)
• Transplantation, Heterologous
• Tumor Hypoxia