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

  • NORLUX Neuro-Oncology Laboratory
July 01, 2012 By:
  • Viel T
  • Talasila KM
  • Monfared P
  • Wang J
  • Jikeli JF
  • Waerzeggers Y
  • Neumaier B
  • Backes H
  • Brekka N
  • Thorsen F
  • Stieber D
  • Niclou SP
  • Winkeler A
  • Tavitian B
  • Hoehn M
  • Bjerkvig R
  • Miletic H
  • Jacobs AH.

UNLABELLED: 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 (18)F-FDG, (11)C-methyl-l-methionine ((11)C-MET), and 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-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 (11)C-MET and (18)F-FLT and relatively low uptake of (18)F-FDG. (11)C-MET was an early indicator of vessel remodeling and tumor proliferation. (18)F-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 (11)C-MET and (18)F-FLT and impaired the (18)F-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 (11)C-MET was more sensitive than (18)F-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 (18)F-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.

2012 Jul. J Nucl Med.53(7):1135-45. Epub 2012 Jun 11.
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