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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Goncalves Nunes, Paulo Sergio [1, 2] ; Zhang, Zhengxing [2] ; Kuo, Hsiou-Ting [2] ; Zhang, Chengcheng [2] ; Rousseau, Julie [2] ; Rousseau, Etienne [2] ; Lau, Joseph [2] ; Kwon, Daniel [2] ; Carvalho, Ivone [1] ; Benard, Francois [3, 2, 4] ; Lin, Kuo-Shyan [3, 2, 4]
Total Authors: 11
[1] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Ribeirao Preto, SP - Brazil
[2] BC Canc Agcy, Dept Mol Oncol, 675 West 10th Ave, Rm 4-123, Vancouver, BC V5Z 1L3 - Canada
[3] Univ British Columbia, Dept Radiol, Vancouver, BC - Canada
[4] BC Canc Agcy, Dept Funct Imaging, Vancouver, BC - Canada
Total Affiliations: 4
Document type: Journal article
Web of Science Citations: 0

2-Nitroimidazole-based hypoxia imaging tracers such as F-18-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, F-18-AmBF3-Bu-2NI, could have the potential to image tumor hypoxia at earlier time points. AmBF3-Bu-2NI was prepared in 4 steps. F-18 labeling was conducted via F-18-F-19 isotope exchange reaction, and F-18-AmBF3-Bu-2NI was obtained in 14.8 +/- 0.4% (n=3) decay-corrected radiochemical yield with 24.5 +/- 5.2GBq/mol specific activity and >99% radiochemical purity. Imaging and biodistribution studies in HT-29 tumor-bearing mice showed that F-18-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 3hours post-injection due to low tumor uptake (0.54 +/- 0.13 and 0.19 +/- 0.04%ID/g at 1 and 3hours post-injection, respectively). The low tumor uptake is likely due to the highly hydrophilic motif of ammoniomethyl-trifluoroborate that prevents free diffusion of F-18-AmBF3-Bu-2NI across the cell membrane. Our results suggest that highly hydrophilic F-18-labeled ammoniomethyl-trifluoroborate derivatives might not be suitable for imaging intracellular targets including nitroreductase, a common tumor hypoxia imaging target. (AU)

FAPESP's process: 17/04599-5 - Novel fluoro-quinazoline derivatives bearing a bioreductive group for tumoral hypoxia diagnosis
Grantee:Paulo Sérgio Gonçalves Nunes
Support type: Scholarships abroad - Research Internship - Doctorate