PET imaging of the dopamine transporter with 18F-FECNT: A polar radiometabolite confounds brain radioligand measurements

Sami S. Zoghbi, H. Umesha Shetty, Masanori Ichise, Masahiro Fujita, Masao Imaizumi, Jeih San Liow, Jay Shah, John L. Musachio, Victor W. Pike, Robert B. Innis

Research output: Contribution to journalArticlepeer-review

161 Scopus citations


18F-2β-Carbomethoxy-3β-(4-chlorophenyl) -8-(2-fluoroethyl)-nortropane (18F-FECNT), a PET radioligand for the dopamine transporter (DAT), generates a radiometabolite that enters the rat brain. The aims of this study were to characterize this radiometabolite and to determine whether a similar phenomenon occurs in human and nonhuman primate brains by examining the stability of the apparent distribution volume in DAT-rich (striatum) and DAT-poor (cerebellum) regions of the brain. Methods: Two rats were infused with 18F-FECNT and sacrificed at 60 min. Extracts of brain and plasma were analyzed by high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometric (LC-MS) techniques. Two human participants and 3 rhesus monkeys were injected with 18F-FECNT and scanned kinetically, with serial arterial blood analysis. Results: At 60 min after the injection of rats, 18F-FECNT accumulated to levels about 7 times higher in the striatum than in the cortex and cerebellum. The radiometabolite was distributed at equal concentrations in all brain regions. The LC-MS techniques identified N-dealkylated FECNT as a major metabolite in the rat brain, and reverse-phase HPLC detected an equivalent amount of radiometabolite eluting with the void volume. The radiometabolite likely was 18F-fluoroacetaldehyde, the product expected from the N-dealkylation of 18F-FECNT, or its oxidation product, 18F-fluoroacetic acid. The distribution volume in the cerebellum increased up to 1.7-fold in humans between 60 and 300 min after injection and 2.0 ± 0.1-fold (mean ± SD; n = 3) in nonhuman primates between 60 and 240 min after injection. Conclusion: An 18F-fluoroalkyl metabolite of 18F-FECNT originating in the periphery confounded the measurements of DAT in the rat brain with a reference tissue model. Its uniform distribution across brain regions suggests that it has negligible affinity for DAT (i.e., it is an inactive radiometabolite). Consistent with the rodent data, the apparent distribution volume in the cerebellum of both humans and nonhuman primates showed a continual increase at late times after injection, a result that may be attributed to entry of the radiometabolite into the brain. Thus, reference tissue modeling of 18F-FECNT will be prone to more errors than analysis with a measured arterial input function.

Original languageEnglish (US)
Pages (from-to)520-527
Number of pages8
JournalJournal of Nuclear Medicine
Issue number3
StatePublished - Mar 1 2006


  • Dopamine transporter
  • F-2β- carbomethoxy-3β-(4-chlorophenyl)-8-(2-fluoroethyl) nortropane
  • In vivo metabolism
  • Receptor

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging


Dive into the research topics of 'PET imaging of the dopamine transporter with 18F-FECNT: A polar radiometabolite confounds brain radioligand measurements'. Together they form a unique fingerprint.

Cite this