PT  - JOURNAL ARTICLE
AU  - Viel, Thomas
AU  - Talasila, Krishna M.
AU  - Monfared, Parisa
AU  - Wang, Jian
AU  - Jikeli, Jan F.
AU  - Waerzeggers, Yannic
AU  - Neumaier, Bernd
AU  - Backes, Heiko
AU  - Brekka, Narve
AU  - Thorsen, Frits
AU  - Stieber, Daniel
AU  - Niclou, Simone P.
AU  - Winkeler, Alexandra
AU  - Tavitian, Bertrand
AU  - Hoehn, Mathias
AU  - Bjerkvig, Rolf
AU  - Miletic, Hrvoje
AU  - Jacobs, Andreas H.
TI  - Analysis of the Growth Dynamics of Angiogenesis-Dependent and -Independent Experimental Glioblastomas by Multimodal Small-Animal PET and MRI
AID  - 10.2967/jnumed.111.101659
DP  - 2012 Jul 01
TA  - Journal of Nuclear Medicine
PG  - 1135--1145
VI  - 53
IP  - 7
4099  - http://jnm.snmjournals.org/content/53/7/1135.short
4100  - http://jnm.snmjournals.org/content/53/7/1135.full
SO  - J Nucl Med2012 Jul 01; 53
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.