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Contents PET Imaging in Glioma: The Neuro-Oncologists Expectations 117 Andreas F. Hottinger, Marc Levivier, Laura Negretti, Krisztian Homicsko, and Roger Stupp PET-imaging is a useful tool for management of certain glioma patients. The variable availability of adequate tracers, their short half-life, but also administrative obstacles and financial constraints are hampering the prospective evaluation of PET. Its im- pact in tumor localization and accurate diagnosis, in treatment response evaluation and ultimately patient outcome needs to be demonstrated. Systematic algorithms for optimal and economical use are needed. We summarize the limitations of the usual imaging techniques, and of the added value of PET-imaging in specific clinical situations. We call for prospective studies and registries rather than the current largely resource-driven use of this valuable technique. Overview of PET Tracers for BrainTumor Imaging 129 Akash SharmaandJonathan McConathy This article provides an overview of the key considerations for the development and application of molecular imaging agents for brain tumors and the major classes of PET tracers that have been used for imaging brain tumors in humans. The mecha- nisms of uptake, biological implications, primary applications, and limitations of PET tracers in neuro-oncology are reviewed. The available data indicate that several of these classes of tracers, including radiolabeled amino acids, have imaging prop- erties superior to those of 18 F-fluorodeoxyglucose, and can complement contrast- enhanced magnetic resonance imaging in the evaluation of brain tumors. FET PET in Neuro-oncology and in Evaluation of Treatment Response 147 Vincent Dunet and John O. Prior Morphologic magnetic resonance imaging is the mainstay in the diagnosis and follow-up of primary brain tumor. However, it has limited ability to differentiate tumor from edema, necrosis, or fibrosis. PET with 18 F-fluoro-ethyl-tyrosine (FET) is a prom- ising and complementary diagnostic and prognostic tool to probe tumor biology in vivo. This article presents the tracer biology and uptake mechanism, the imaging protocol and quantitative image analysis, common pitfalls and variants, and the main indications for FET PET. Finally, a summary on what the referring physician needs to know about FET PET is presented. Magnetic Resonance Imaging of Glioma in the Era of Antiangiogenic Therapy 163 Sarah N. Khan, Michael Linetsky, Benjamin M. Ellingson, and Whitney B. Pope Since it supplanted computed tomography in the early 1990s, magnetic resonance (MR) imaging has remained the standard tool to evaluate disease status in patients with brain tumors. With the recent adoption of antiangiogenic therapy for gliomas, it has become increasingly clear that leakiness of the blood-brain barrier, the physiologic correlate of contrast enhancement, is affected by a multitude of patho- physiologic processes, not all of which correlate with tumor burden. To address this issue, physiologic imaging including diffusion and perfusion MR imaging has been investigated as an avenue to acquire predictive and prognostic biomarkers useful in the evaluation of high-grade gliomas. PET Imaging of Brain Tumors

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PET Imaging of Brain Tumors

Contents

PET Imaging in Glioma:The Neuro-Oncologist’s Expectations 117

Andreas F. Hottinger, Marc Levivier, Laura Negretti, Krisztian Homicsko, and Roger Stupp

PET-imaging is a useful tool for management of certain glioma patients. The variableavailability of adequate tracers, their short half-life, but also administrative obstaclesand financial constraints are hampering the prospective evaluation of PET. Its im-pact in tumor localization and accurate diagnosis, in treatment response evaluationand ultimately patient outcome needs to be demonstrated. Systematic algorithmsfor optimal and economical use are needed. We summarize the limitations of theusual imaging techniques, and of the added value of PET-imaging in specific clinicalsituations. We call for prospective studies and registries rather than the currentlargely resource-driven use of this valuable technique.

Overview of PET Tracers for BrainTumor Imaging 129

Akash SharmaandJonathanMcConathy

This article provides an overview of the key considerations for the development andapplication of molecular imaging agents for brain tumors and the major classes ofPET tracers that have been used for imaging brain tumors in humans. The mecha-nisms of uptake, biological implications, primary applications, and limitations ofPET tracers in neuro-oncology are reviewed. The available data indicate that severalof these classes of tracers, including radiolabeled amino acids, have imaging prop-erties superior to those of 18F-fluorodeoxyglucose, and can complement contrast-enhanced magnetic resonance imaging in the evaluation of brain tumors.

FET PET in Neuro-oncology and in Evaluation ofTreatment Response 147

Vincent Dunet andJohnO. Prior

Morphologic magnetic resonance imaging is the mainstay in the diagnosis andfollow-up of primary brain tumor. However, it has limited ability to differentiate tumorfrom edema, necrosis, or fibrosis. PET with 18F-fluoro-ethyl-tyrosine (FET) is a prom-ising and complementary diagnostic and prognostic tool to probe tumor biologyin vivo. This article presents the tracer biology and uptake mechanism, the imagingprotocol and quantitative image analysis, common pitfalls and variants, and themainindications for FET PET. Finally, a summary on what the referring physician needs toknow about FET PET is presented.

Magnetic Resonance Imaging of Glioma in the Era of Antiangiogenic Therapy 163

SarahN. Khan,Michael Linetsky, BenjaminM. Ellingson, and Whitney B. Pope

Since it supplanted computed tomography in the early 1990s, magnetic resonance(MR) imaging has remained the standard tool to evaluate disease status in patientswith brain tumors. With the recent adoption of antiangiogenic therapy for gliomas,it has become increasingly clear that leakiness of the blood-brain barrier, thephysiologic correlate of contrast enhancement, is affected by a multitude of patho-physiologic processes, not all of which correlate with tumor burden. To address thisissue, physiologic imaging including diffusion and perfusion MR imaging has beeninvestigated as an avenue to acquire predictive and prognostic biomarkers usefulin the evaluation of high-grade gliomas.

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Application of Advanced MR Imaging Techniques and the Evolving Role of PET/MRImaging in Neuro-oncology 183

Thomas C. Kwee andMaarten L. Donswijk

A requisite to achieve a better outcome in patients with high-grade glioma is thedevelopment of noninvasive imaging techniques that improve tumor detection,delineation, and grading, before, during, and after therapy. This article reviews thevalue of a selection of important advanced MR imaging techniques (diffusion-weighted MR imaging, diffusion-tensor imaging, perfusion MR imaging, and MRspectroscopy) and the evolving role of positron emission tomography (PET)/MRimaging in the evaluation of high-grade gliomas in various settings. This review intro-duces the reader to the basic principles and clinical applications of these advancedMR imaging and PET/MR imaging techniques.

PET Parametric Response Mapping for Clinical Monitoring andTreatment ResponseEvaluation in BrainTumors 201

BenjaminM. Ellingson, Wei Chen, RobertJ. Harris, Whitney B. Pope, Albert Lai,Phioanh L. Nghiemphu, Johannes Czernin, Michael E. Phelps, and Timothy F. Cloughesy

PET parametric response maps (PRMs) are a provocative new molecular imagingtechnique for quantifying brain tumor response to therapy in individual patients.By aligning sequential PET scans over time using anatomic MR imaging information,the voxel-wise change in radiotracer uptake can be quantified and visualized. PETPRMs can be performed before and after a particular therapy to test whether thetumor is responding favorably, or performed relative to a distant time point tomonitor changes through the course of a treatment. This article focuses on manyof the technical details involved in generating, visualizing, and quantifying PETPRMs, and practical applications and example case studies.

Novel Quantitative Techniques in Hybrid (PET-MR) Imaging of Brain Tumors 219

Srinivasan Senthamizhchelvan andHabib Zaidi

Brain tumors are a collection of heterogeneous intracranial neoplasms. MolecularPET and anatomic MR imaging together can provide reliable quantitative informationon tumor characterization, and help in treatment planning and monitoring therapeu-tic evaluation, noninvasively. Coregistration of MRI and PET images have beensuccessfully used to improve diagnostic accuracy and in evaluating treatment re-sponse. Whole-body PET-MR scanners capable of assessing morphologic, meta-bolic, and functional information simultaneously are now commercially available.Early clinical studies speculate that PET-MR will be useful in several clinical special-ties. In this report, we highlight the advances and applications of hybrid PET-MR inquantitative brain tumor imaging.

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