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

Author(s):Show less -

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]}

Affiliation

^[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

• Document type: Journal article
• Source: JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS; v. 61, n. 4, p. 370-379, APR 2018.
• Web of Science Citations: 0

Abstract

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 Opportunities: Scholarships abroad - Research Internship - Doctorate