A glioblastoma multiforme tumor mouse model for testing novel brain tracers

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Ziel/Aim The aim of this work was to establish and characterize a glioblastoma multiforme (GBM) mouse model with different orthotopic tumors by imaging as a basis for future in vivo testing of novel brain tracers and radiotherapeutics. Methodik/Methods Nineteen eight-week-old female GBM (U-87MG or U-373) bearing CB17-SCID mice were examined weekly with T2w 3T MRI to monitor tumor growth. For viability testing, O-(2-[F-18]-fluoroethyl)-l-tyrosine (FET) small animal PET/CT was performed at different tumor sizes. For pilot tracer testing [Tc-99m]Tc-Tetrofosmin (TTF) was administered intravenously, and successive SPECT/CT imaging was performed up to 24 hours. Ergebnisse/Results U-87MG produced rapidly and solidly growing GBM tumors that were easily delineated by MRI. U-373 tumors were detectable 1-2 weeks later than U-87MG and grew more diffuse and invasive. FET PET showed clearly visible uptake in U-373 and U-87MG tumors with a tumor to background ratio (TBR)>3. In comparison, TTF uptake was not always visible but in case of U-87MG still detectable. In ten cases, the tumor formed both an intracranial and a peripheral part in which the uptake of TTF differed depending on the region. The TBR of the peripheral part was 4.3 and 3.4 for U-87MG and U-373, respectively. The TBR of the intracranial part was 1.4 and 1.0 for U-87MG and U-373, respectively while the intracranial tumor to liver ratio was<0.1 in all tumors. Schlussfolgerungen/Conclusions Both glioblastoma cell lines started growing reliably and could be monitored by MR imaging. Due to highly invasive growth, U-373 tumors were more difficult to measure than U-87MG. FET provided good delineation of the GBM tumors and confirmed their functional integrity. The general condition of the mice was good, even when the tumor size approached the critical end point of 80 µL. TTF was tested as pilot brain tracer, and tumor uptake parameters were collected as reference for future studies of novel theranostics. Publication History Article published online: 30 March 2023 © 2023. Thieme. All rights reserved. Georg Thieme Verlag Rüdigerstraße 14, 70469 Stuttgart, Germany

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