3 years ago

Synthesis and evaluation of an 18F-labeled trifluoroborate derivative of 2-nitroimidazole for imaging tumor hypoxia with positron emission tomography

François Bénard, Julie Rousseau, Chengcheng Zhang, Kuo-Shyan Lin, Joseph Lau, Zhengxing Zhang, Daniel Kwon, Hsiou-Ting Kuo, Paulo Sérgio Gonçalves Nunes, Etienne Rousseau, Ivone Carvalho
2-Nitroimidazole-based hypoxia imaging tracers such as 18F-FMISO are normally imaged at late time points (several hours post-injection) due to their slow clearance from background tissues. Here we investigated if a hydrophilic zwitterion-based ammoniomethyl-trifluoroborate derivative of 2-nitroimidazole, 18F-AmBF3-Bu-2NI, could have the potential to image tumor hypoxia at earlier time points. AmBF3-Bu-2NI was prepared in four steps. 18F labeling was conducted via 18F-19F isotope exchange reaction, and 18F-AmBF3-Bu-2NI was obtained in 14.8 ± 0.4% (n = 3) decay-corrected radiochemical yield with 24.5 ± 5.2 GBq/μmol specific activity and > 99% radiochemical purity. Imaging and biodistribution studies in HT-29 tumor-bearing mice showed that 18F-AmBF3-Bu-2NI cleared quickly from blood, and was excreted via the hepatobiliary and renal pathways. However, the tumor was not visualized in PET images until 3 h post-injection due to low tumor uptake (0.54 ± 0.13 and 0.19 ± 0.04%ID/g at 1 h and 3 h post-injection, respectively). The low tumor uptake is likely due to the highly hydrophilic motif of ammoniomethyl-trifluoroborate that prevents free diffusion of 18F-AmBF3-Bu-2NI across the cell membrane. Our results suggest that highly hydrophilic 18F-labeled ammoniomethyl-trifluoroborate derivatives might not be suitable for imaging intracellular targets including nitroreductase, a common tumor hypoxia imaging target.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/jlcr.3594

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