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Tracer Level Electrophilic Synthesis and Pharmacokinetics of the Hypoxia Tracer [F-18]EF5

Eskola, Olli; Gronroos, Tove J.; Forsback, Sarita; Tuomela, Johanna; Komar, Gaber; Bergman, Jorgen; Härkönen, Pirkko LU ; Haaparanta, Merja; Minn, Heikki and Solin, Olof (2012) In Molecular Imaging and Biology 14(2). p.205-212
Abstract
2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)-acetamide labeled with [F-18]-fluorine ([F-18]EF5), a promising tracer for tumor hypoxia, has previously been synthesized in low yields and low specific radioactivity. In pharmacokinetic evaluations, in the presence of non-radioactive EF5, a uniform and low background uptake and high in vivo stability of [F-18]EF5 have been demonstrated. Our purpose was to increase the specific radioactivity of [F-18]EF5 to enable to study the pharmacokinetics at trace level. [F-18]EF5 was synthesized using high specific radioactivity electrophilic [F-18]F-2 as labelling reagent. Biodistribution of [F-18]EF5 was determined in a prostate tumor mouse model, and formation of radiolabelled... (More)
2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)-acetamide labeled with [F-18]-fluorine ([F-18]EF5), a promising tracer for tumor hypoxia, has previously been synthesized in low yields and low specific radioactivity. In pharmacokinetic evaluations, in the presence of non-radioactive EF5, a uniform and low background uptake and high in vivo stability of [F-18]EF5 have been demonstrated. Our purpose was to increase the specific radioactivity of [F-18]EF5 to enable to study the pharmacokinetics at trace level. [F-18]EF5 was synthesized using high specific radioactivity electrophilic [F-18]F-2 as labelling reagent. Biodistribution of [F-18]EF5 was determined in a prostate tumor mouse model, and formation of radiolabelled metabolites was studied in mouse, rat and human plasma. On average, 595 +/- 153 MBq of [F-18]EF5 was produced. Specific radioactivity was 6.6 +/- 1.9 GBq/mu mol and the radiochemical purity exceeded 99.0%. [F-18]EF5 was distributed uniformly in tissues, with highest uptake in liver, kidney, and intestine. Several radiolabelled metabolites were detected in mouse plasma and tissues, whereas low amounts of metabolites were detected in human and rat plasma. [F-18]EF5 was synthesized by electrophilic labelling with high quality and high yields. Pharmacokinetics of [F-18]EF5 was determined at trace level in several species. Our results suggest that the trace-level approach does not affect the biodistribution of [F-18]EF5. Extensive metabolism was seen in mouse. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Hypoxia, Biodistribution, Metabolism, PET, [F-18]EF5, Electrophilic synthesis
in
Molecular Imaging and Biology
volume
14
issue
2
pages
205 - 212
publisher
Springer
external identifiers
  • wos:000301584100008
  • scopus:84861481324
ISSN
1536-1632
DOI
10.1007/s11307-011-0484-4
language
English
LU publication?
yes
id
9676a94f-65a4-4e38-8db0-44de95875807 (old id 2515418)
date added to LUP
2012-05-07 15:42:30
date last changed
2017-04-09 03:17:03
@article{9676a94f-65a4-4e38-8db0-44de95875807,
  abstract     = {2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)-acetamide labeled with [F-18]-fluorine ([F-18]EF5), a promising tracer for tumor hypoxia, has previously been synthesized in low yields and low specific radioactivity. In pharmacokinetic evaluations, in the presence of non-radioactive EF5, a uniform and low background uptake and high in vivo stability of [F-18]EF5 have been demonstrated. Our purpose was to increase the specific radioactivity of [F-18]EF5 to enable to study the pharmacokinetics at trace level. [F-18]EF5 was synthesized using high specific radioactivity electrophilic [F-18]F-2 as labelling reagent. Biodistribution of [F-18]EF5 was determined in a prostate tumor mouse model, and formation of radiolabelled metabolites was studied in mouse, rat and human plasma. On average, 595 +/- 153 MBq of [F-18]EF5 was produced. Specific radioactivity was 6.6 +/- 1.9 GBq/mu mol and the radiochemical purity exceeded 99.0%. [F-18]EF5 was distributed uniformly in tissues, with highest uptake in liver, kidney, and intestine. Several radiolabelled metabolites were detected in mouse plasma and tissues, whereas low amounts of metabolites were detected in human and rat plasma. [F-18]EF5 was synthesized by electrophilic labelling with high quality and high yields. Pharmacokinetics of [F-18]EF5 was determined at trace level in several species. Our results suggest that the trace-level approach does not affect the biodistribution of [F-18]EF5. Extensive metabolism was seen in mouse.},
  author       = {Eskola, Olli and Gronroos, Tove J. and Forsback, Sarita and Tuomela, Johanna and Komar, Gaber and Bergman, Jorgen and Härkönen, Pirkko and Haaparanta, Merja and Minn, Heikki and Solin, Olof},
  issn         = {1536-1632},
  keyword      = {Hypoxia,Biodistribution,Metabolism,PET,[F-18]EF5,Electrophilic synthesis},
  language     = {eng},
  number       = {2},
  pages        = {205--212},
  publisher    = {Springer},
  series       = {Molecular Imaging and Biology},
  title        = {Tracer Level Electrophilic Synthesis and Pharmacokinetics of the Hypoxia Tracer [F-18]EF5},
  url          = {http://dx.doi.org/10.1007/s11307-011-0484-4},
  volume       = {14},
  year         = {2012},
}