PET imaging of medulloblastoma with an 18F-labeled tryptophan analogue in a transgenic mouse model

Sci Rep. 2020 Mar 2;10(1):3800. doi: 10.1038/s41598-020-60728-6.

Abstract

In vivo positron emission tomography (PET) imaging is a key modality to evaluate disease status of brain tumors. In recent years, tremendous efforts have been made in developing PET imaging methods for pediatric brain tumors. Carbon-11 labelled tryptophan derivatives are feasible as PET imaging probes in brain tumor patients with activation of the kynurenine pathway, but the short half-life of carbon-11 limits its application. Using a transgenic mouse model for the sonic hedgehog (Shh) subgroup of medulloblastoma, here we evaluated the potential of the newly developed 1-(2-[18F]fluoroethyl)-L-tryptophan (1-L-[18F]FETrp) as a PET imaging probe for this common malignant pediatric brain tumor. 1-L-[18F]FETrp was synthesized on a PETCHEM automatic synthesizer with good chemical and radiochemical purities and enantiomeric excess values. Imaging was performed in tumor-bearing Smo/Smo medulloblastoma mice with constitutive actvation of the Smoothened (Smo) receptor using a PerkinElmer G4 PET-X-Ray scanner. Medulloblastoma showed significant and specific accumulation of 1-L-[18F]FETrp. 1-L-[18F]FETrp also showed significantly higher tumor uptake than its D-enantiomer, 1-D-[18F]FETrp. The uptake of 1-L-[18F]FETrp in the normal brain tissue was low, suggesting that 1-L-[18F]FETrp may prove a valuable PET imaging probe for the Shh subgroup of medulloblastoma and possibly other pediatric and adult brain tumors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport
  • Brain Neoplasms / diagnostic imaging*
  • Fluorine Radioisotopes / chemistry*
  • Fluorine Radioisotopes / metabolism
  • Humans
  • Medulloblastoma / diagnostic imaging*
  • Medulloblastoma / metabolism
  • Mice
  • Mice, Transgenic
  • Positron-Emission Tomography
  • Radiopharmaceuticals / chemistry*
  • Radiopharmaceuticals / metabolism
  • Tryptophan / analogs & derivatives*
  • Tryptophan / metabolism

Substances

  • Fluorine Radioisotopes
  • Radiopharmaceuticals
  • Tryptophan
  • Fluorine-18