In Response: The comment by Pallini and colleagues points toward some interesting aspects that have not been addressed in detail in our study (1). We are therefore happy to respond to their comments.

In general, the magnetic resonance image (MRI) appearance of glioblastomas (GBM) induced by inoculation of nude mice with human cancer stem cell (CSC) lines has neither been characterized nor correlated with histological features. According to the observations we made on more than 50 mice, MRI appearance mirrors the intra- and intertumoral variability of xenografts (e.g., cyst-like growth pattern or meningeal metastasis resulting in a hydrocephalic configuration of the ventricles). As strict institutional guidelines preclude suffering of the animals, we sacrificed them before the ventricles were displaced or compressed. Thus, tumors hardly grew long enough to form necrosis. Considering that any signs of the implantation procedure should have vanished after 12 weeks (2), it may safely be assumed that the observed changes are tumor related. This result could, in principle, also explain an increased T2 signal due to regressive changes. However, in our opinion, Pallini and colleagues may have misinterpreted the upper right panel of our Fig. 6A. Here, as in all other xenografts, the T2 signal of the untreated tumor was definitively lower as compared to the third ventricle (Fig. 1). We would further like to stress that the key message of our manuscript is not affected by this issue. The alternative interpretation by Pallini and colleagues who suggest that temozolomide might have induced a transient reduction of the proliferation rate appears plausible to us and is in line with our overall conclusion that temozolomide may deplete GBM CSC. We thus agree that further studies are required to fully understand how temozolomide acts on CSC and why temozolomide-susceptible CSC can resist the treatment in vivo.

Figure 1.

The complete T2-weighted series of the animal shown in the upper right panel of Fig. 6A in our report is given.

Figure 1.

The complete T2-weighted series of the animal shown in the upper right panel of Fig. 6A in our report is given.

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C.P. Beier: travel support, Schering-Plough. The other authors disclosed no potential conflicts of interest.

1
Beier D, Röhrl S, Pillai DR, et al. Temozolomide preferentially depletes cancer stem cells in glioblastoma.
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Knight RA, Han Y, Nagaraja TN, et al. Temporal MRI assessment of intracerebral hemorrhage in rats.
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