Analysis of the growth dynamics of angiogenesis-dependent and -independent experimental glioblastomas by multimodal small-animal PET and MRI

Thomas Viel, Krishna M. Talasila, Parisa Monfared, Jian Wang, Jan F. Jikeli, Yannic Waerzeggers, Bernd Neumaier, Heiko Backes, Narve Brekka, Frits Thorsen, Daniel Stieber, Simone P. Niclou, Alexandra Winkeler, Bertrand Tavitian, Mathias Hoehn, Rolf Bjerkvig, Hrvoje Miletic, Andreas H. Jacobs*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

28 Citations (Scopus)

Abstract

The hypothesis of this study was that distinct experimental glioblastoma phenotypes resembling human disease can be noninvasively distinguished at various disease stages by imaging in vivo. Methods: Cultured spheroids from 2 human glioblastomas were implanted into the brains of nude rats. Glioblastoma growth dynamics were followed by PET using 18F-FDG, 11C-methyl-L-methionine (11C-MET), and 3′-deoxy-3′-18F-fluorothymidine (18F-FLT) and by MRI at 3-6 wk after implantation. For image validation, parameters were coregistered with immunohistochemical analysis. Results: Two tumor phenotypes (angiogenic and infiltrative) were obtained. The angiogenic phenotype showed high uptake of 11C-MET and 18F-FLT and relatively low uptake of 18F-FDG. 11C-MET was an early indicator of vessel remodeling and tumor proliferation. 18F-FLT uptake correlated to positive Ki67 staining at 6 wk. T1- and T2-weighted MR images displayed clear tumor delineation with strong gadolinium enhancement at 6 wk. The infiltrative phenotype did not accumulate 11C-MET and 18F-FLT and impaired the 18F-FDG uptake. In contrast, the Ki67 index showed a high proliferation rate. The extent of the infiltrative tumors could be observed by MRI but with low contrast. Conclusion: For angiogenic glioblastomas, noninvasive assessment of tumor activity corresponds well to immunohistochemical markers, and 11C-MET was more sensitive than 18F-FLT at detecting early tumor development. In contrast, infiltrative glioblastoma growth in the absence of blood-brain barrier breakdown is difficult to noninvasively follow by existing imaging techniques, and a negative 18F-FLT PET result does not exclude the presence of proliferating glioma tissue. The angiogenic model may serve as an advanced system to study imaging-guided antiangiogenic and antiproliferative therapies.

Original languageEnglish
Pages (from-to)1135-1145
Number of pages11
JournalJournal of Nuclear Medicine
Volume53
Issue number7
DOIs
Publication statusPublished - 1 Jul 2012

Keywords

  • Angiogenesis
  • Glioblastoma
  • Infiltration
  • MRI
  • PET

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