**8. Hypoxia-based probes**

Hypoxia, a hallmark of aggressive tumor behavior often noted in high grade glioblastomas, is associated with resistance to therapy, poorer survival, invasion and aggressiveness (Szeto et al. 2009). Estimation of hypoxia could be an important determinant of overall survival in several tumors including gliomas. PET imaging with the hypoxia radiotracer [18F]fluoromisonidazole ([18F]FMISO) presents a possible means of noninvasively detecting tumor hypoxia in gliomas (Rasey et al. 2000; Valk et al. 1992). In a preclinical C6 glioma tumor model study (Tochon-Danguy et al. 2002), [18F]FMISO uptake was significantly higher in tumor tissue compared to normal brain and the uptake was independent of tumor size. [18F]FMISO uptake was observed homogeneously throughout viable glioma tissue in tumor sizes ranging from 2 mm to almost 1 cm. Quantitation of uptake of [18F]FMISO

PET Imaging of Gliomas 173

limited to detecting meningiomas, while hypoxia markers are best suited for disease prognosis and predicting response to radiotherapy. Recent studies with choline-, acetateand integrin-based PET probes seem encouraging but more work is needed to fully appreciate their potential. In conclusion, positron-labeled amino acids are showing highest general utility for staging and therapy management of gliomas, while other metabolic probes are undergoing validation to answer selected clinical questions such as assessment of

The authors thank Drs. Sandi A. Kwee and Laura Horky for their contributions. The work was supported by the US Department of Energy (DE-FG02-10ER41691, (TRD)) and NIH

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**11. Acknowledgement** 

(R21 EB0110085 (TRD)).

**12. References** 

showed a tumor-to-brain ratio of 1.9 and a tumor-to-blood ratio of 2.6 at 2 hours postinjection. In a recent clinical study by Shibahara et al. (2010), 8 patients with gliomas of different grades underwent PET studies with a new imidazole based hypoxia imaging agent, 1-(2-[18F]fluoro-1-[hydroxymethyl]ethoxy)methyl-2-nitroimidazole ([18F]FRP-170). The new agent showed higher image contrast and faster clearance than [18F]FMISO. [18F]FRP-170 images showed positive correlation with HIF-1 expression, a weak correlation with [18F]FDG-PET and MR, but no correlation with [11C]MET-PET. The [18F]FRP-170-PET images showed marked uptake in the 3 GBM, and moderate uptake in recurrent anaplastic astrocytoma and oligodendroglioma, but no uptake in the other tumors (oligodendroglioma and diffuse astrocytoma). It is suggested that the use of hypoxia markers in patients with primary or recurrent gliomas could potentially assist in defining hypoxic tumor regions and predicting response to radiotherapy, but is not effective for grading tumors.
