AbstractIn 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.