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

• Published in: Scientific reports Vol. 10; no. 1; p. 3800
• Main Authors: Xin, Yangchun, Yue, Xuyi, Li, Hua, Li, Zhiqin, Cai, Hancheng, Choudhary, Arabinda K., Zhang, Shaohui, Chugani, Diane C., Langhans, Sigrid A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 02.03.2020; Nature Publishing Group UK
• Subjects: Brain cancer; Brain tumors; Enantiomers; Hedgehog protein; Medulloblastoma; Neuroimaging; Pediatrics; Positron emission tomography; Rodents; Tomography; Transgenic mice; Tryptophan; Tumors
• ISSN: 2045-2322; 2045-2322
• 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-[ 18 F]fluoroethyl)-L-tryptophan (1-L-[ 18 F]FETrp) as a PET imaging probe for this common malignant pediatric brain tumor. 1-L-[ 18 F]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-[ 18 F]FETrp. 1-L-[ 18 F]FETrp also showed significantly higher tumor uptake than its D-enantiomer, 1-D-[ 18 F]FETrp. The uptake of 1-L-[ 18 F]FETrp in the normal brain tissue was low, suggesting that 1-L-[ 18 F]FETrp may prove a valuable PET imaging probe for the Shh subgroup of medulloblastoma and possibly other pediatric and adult brain tumors.