RT Journal Article
SR Electronic
T1 Analysis of the Growth Dynamics of Angiogenesis-Dependent and -Independent Experimental Glioblastomas by Multimodal Small-Animal PET and MRI
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1135
OP 1145
DO 10.2967/jnumed.111.101659
VO 53
IS 7
A1 Thomas Viel
A1 Krishna M. Talasila
A1 Parisa Monfared
A1 Jian Wang
A1 Jan F. Jikeli
A1 Yannic Waerzeggers
A1 Bernd Neumaier
A1 Heiko Backes
A1 Narve Brekka
A1 Frits Thorsen
A1 Daniel Stieber
A1 Simone P. Niclou
A1 Alexandra Winkeler
A1 Bertrand Tavitian
A1 Mathias Hoehn
A1 Rolf Bjerkvig
A1 Hrvoje Miletic
A1 Andreas H. Jacobs
YR 2012
UL http://jnm.snmjournals.org/content/53/7/1135.abstract
AB 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.