Simultaneous trimodal positron emission tomography/magnetic resonance imaging/electroencephalography (PET/MRI/EEG) resting state (rs) brain data were acquired from 10 healthy male volunteers. The ...rs‐functional MRI (fMRI) metrics, such as regional homogeneity (ReHo), degree centrality (DC) and fractional amplitude of low‐frequency fluctuations (fALFFs), as well as 2‐18Ffluoro‐2‐desoxy‐d‐glucose (FDG)‐PET standardised uptake value (SUV), were calculated and the measures were extracted from the default mode network (DMN) regions of the brain. Similarly, four microstates for each subject, showing the diverse functional states of the whole brain via topographical variations due to global field power (GFP), were estimated from artefact‐corrected EEG signals. In this exploratory analysis, the GFP of microstates was nonparametrically compared to rs‐fMRI metrics and FDG‐PET SUV measured in the DMN of the brain. The rs‐fMRI metrics (ReHO, fALFF) and FDG‐PET SUV did not show any significant correlations with any of the microstates. The DC metric showed a significant positive correlation with microstate C (rs = 0.73, p = .01). FDG‐PET SUVs indicate a trend for a negative correlation with microstates A, B and C. The positive correlation of microstate C with DC metrics suggests a functional relationship between cortical hubs in the frontal and occipital lobes. The results of this study suggest further exploration of this method in a larger sample and in patients with neuropsychiatric disorders. The aim of this exploratory pilot study is to lay the foundation for the development of such multimodal measures to be applied as biomarkers for diagnosis, disease staging, treatment response and monitoring of neuropsychiatric disorders.
Amino Acid PET in Neurooncology Galldiks, Norbert; Lohmann, Philipp; Fink, Gereon R ...
Journal of Nuclear Medicine,
05/2023, Volume:
64, Issue:
5
Journal Article
Peer reviewed
Open access
For decades, several amino acid PET tracers have been used to optimize diagnostics in patients with brain tumors. In clinical routine, the most important clinical indications for amino acid PET in ...brain tumor patients are differentiation of neoplasm from nonneoplastic etiologies, delineation of tumor extent for further diagnostic and treatment planning (i.e., diagnostic biopsy, resection, or radiotherapy), differentiation of treatment-related changes such as pseudoprogression or radiation necrosis after radiation or chemoradiation from tumor progression at follow-up, and assessment of response to anticancer therapy, including prediction of patient outcome. This continuing education article addresses the diagnostic value of amino acid PET for patients with either glioblastoma or metastatic brain cancer.
The most common type of primary brain tumor is malignant glioma. Despite intensive therapeutic efforts, the majority of these neoplasms remain incurable. Imaging techniques are important for initial ...tumor detection and comprise indispensable tools for monitoring treatment. Structural imaging using contrast-enhanced MRI is the method of choice for brain tumor surveillance, but its capacity to differentiate tumor from nonspecific tissue changes can be limited, particularly with posttreatment gliomas. Metabolic imaging using positron-emission-tomography (PET) can provide relevant additional information, which may allow for better assessment of tumor burden in ambiguous cases. Specific PET tracers have addressed numerous molecular targets in the last decades, but only a few have achieved relevance in routine clinical practice. At present, PET studies using radiolabeled amino acids appear to improve clinical decision-making as these tracers can offer better delineation of tumor extent as well as improved targeting of biopsies, surgical interventions, and radiation therapy. Amino acid PET imaging also appears useful for distinguishing glioma recurrence or progression from postradiation treatment effects, particularly radiation necrosis and pseudoprogression, and provides information on histological grading and patient prognosis. In the last decade, the tracers O-(2-(18)Ffluoroethyl)-L-tyrosine (FET) and 3,4-dihydroxy-6-(18)F-fluoro-L-phenylalanine (FDOPA) have been increasingly used for these indications. This review article focuses on these tracers and summarizes their recent applications for patients with brain tumors. Current uses of tracers other than FET and FDOPA are also discussed, and the most frequent practical questions regarding PET brain tumor imaging are reviewed.
Sodium MRI is a promising method for assessing the metabolic properties of brain tumours. In a recent study, a strong relationship between semi‐quantitative abnormalities in sodium MRI and the ...mutational status of the isocitrate dehydrogenase enzyme (IDH) with untreated cerebral gliomas was observed. Here, sodium relaxometry in brain tumour tissue was investigated in relation to molecular markers in order to reveal quantitative sodium tissue parameters and the differences between healthy tissue and brain tumour. The previous semi‐quantitative approach is extended by use of suitable relaxometry methods accompanied by numerical simulation to achieve detailed quantitative analysis of intra‐ and extracellular sodium concentration using an enhanced SISTINA sequence at 4 T. Using optimised techniques, biexponential sodium relaxation times in tumour (T*2f, T*2s) and in healthy contralateral brain tissue (T*2f,CL, T*2s,CL) were estimated in 10 patients, along with intracellular sodium molar fractions (χ, χCL), volume fractions (η, ηCL) and concentrations (ρin, ρin,CL). The total sodium tissue concentrations (ρT, ρT,CL) were also estimated. The ratios T*2f/T*2f,CL (P = .05), η/ηCL (P = .02) and χ/χCL (P = .02) were significantly lower in IDH mutated than in IDH wildtype gliomas (n = 4 and n = 5 patients, respectively). The Wilcoxon rank‐sum test was used to compare sodium MRI parameters in patients with and without IDH mutation. Thus, quantitative analysis of relaxation rates, intra‐ and extracellular sodium concentrations, intracellular molar and volume fractions based on enhanced SISTINA confirmed a relationship between abnormalities in sodium parameters and the IDH mutational status in cerebral gliomas, hence catering for the potential to provide further insights into the status of the disease.
Sodium relaxometry in brain tumours was investigated in relation to complementing molecular markers to reveal quantitative sodium tissue parameters and the differences between healthy and diseased tissue. Relaxometry methods were employed alongside numerical simulation to achieve quantitative analysis of intra‐ and extracellular sodium concentrations using an enhanced SISTINA sequence at 4 T. The results reveal a relationship between abnormalities in sodium parameters and the IDH mutational status of the tumours, potentially providing greater insight into disease status.
Despite profound advances in treatment approaches, gliomas remain associated with very poor prognoses. The residual cells after incomplete resection often migrate and proliferate giving a seed for ...highly resistant gliomas. The efficacy of chemotherapeutic drugs is often strongly limited by their poor selectivity and the blood brain barrier (BBB). Therefore, the development of therapeutic carrier systems for efficient transport across the BBB and selective delivery to tumor cells remains one of the most complex problems facing molecular medicine and nano‐biotechnology. To address this challenge, a stimuli sensitive nanogel is synthesized using pre‐polymer approach for the effective delivery of nano‐irradiation. The nanogels are cross‐linked via matrix metalloproteinase (MMP‐2,9) substrate and armed with Auger electron emitting drug 5‐125IIodo‐4”‐thio‐2”‐deoxyuridine (125IITdU) which after release can be incorporated into the DNA of tumor cells. Functionalization with diphtheria toxin receptor ligand allows nanogel transcytosis across the BBB at tumor site. Functionalized nanogels efficiently and increasingly explore transcytosis via BBB co‐cultured with glioblastoma cells. The subsequent nanogel degradation correlates with up‐regulated MMP2/9. Released 125IITdU follows the thymidine salvage pathway ending in its incorporation into the DNA of tumor cells. With this concept, a highly efficient strategy for intracellular delivery of radiopharmaceuticals across the challenging BBB is presented.
Matrix metalloprotease (MMP) sensitive nanogels are synthesized for effective delivery of a radiopharmaceutical (125IITdU) across the blood−brain barrier (BBB). The nanogels show efficient transcytosis across the in vitro model of BBB co‐cultured with glioblastoma cells. Once transcytosed, nanogels degrade in an up‐regulated MMP2/9 environment of glioblastoma and release the radiopharmaceutical, which gets incorporated into the DNA of tumor cells by thymidine salvage pathway.
The aim of this study was to give an update on the emerging role of PET using radiolabelled amino acids in the diagnostic workup and management of patients with cerebral gliomas and brain metastases.
...Numerous studies have demonstrated the potential of PET using radiolabelled amino acids for differential diagnosis of brain tumours, delineation of tumour extent for treatment planning and biopsy guidance, differentiation between tumour progression and recurrence versus treatment-related changes, and for monitoring of therapy. The Response Assessment in Neuro-Oncology (RANO) working group - an international effort to develop new standardized response criteria for clinical trials in brain tumours - has recently recommended the use of amino acid PET imaging for brain tumour management in addition to MRI at every stage of disease. With the introduction of F-18 labelled amino acids, a broader clinical application has become possible, but is still hampered by the lack of regulatory approval and of reimbursement in many countries.
PET using radiolabelled amino acids is a rapidly evolving method that can significantly enhance the diagnostic value of MRI in brain tumours. Current developments suggest that this imaging technique will become an indispensable tool in neuro-oncological centres in the near future.
Abstract
The management of patients with glioma usually requires multimodality treatment including surgery, radiotherapy, and systemic therapy. Accurate neuroimaging plays a central role for ...radiotherapy planning and follow-up after radiotherapy completion. In order to maximize the radiation dose to the tumor and to minimize toxic effects on the surrounding brain parenchyma, reliable identification of tumor extent and target volume delineation is crucial. The use of positron emission tomography (PET) for radiotherapy planning and monitoring in gliomas has gained considerable interest over the last several years, but Class I data are not yet available. Furthermore, PET has been used after radiotherapy for response assessment and to distinguish tumor progression from pseudoprogression or radiation necrosis. Here, the Response Assessment in Neuro-Oncology (RANO) working group provides a summary of the literature and recommendations for the use of PET imaging for radiotherapy of patients with glioma based on published studies, constituting levels 1-3 evidence according to the Oxford Centre for Evidence-based Medicine.
Consistent findings postulate disturbed glutamatergic function (more specifically a hypofunction of the ionotropic NMDA receptors) as an important pathophysiologic mechanism in schizophrenia. ...However, the role of the metabotropic glutamatergic receptors type 5 (mGluR5) in this disease remains unclear. In this study, we investigated their significance (using 11CABP688) for psychopathology and cognition in male patients with chronic schizophrenia and healthy controls. In the patient group, lower mGluR5 binding potential (BPND) values in the left temporal cortex and caudate were associated with higher general symptom levels (negative and depressive symptoms), lower levels of global functioning and worse cognitive performance. At the same time, in both groups, mGluR5 BPND were significantly lower in smokers (F27,1 = 15.500; p = .001), but without significant differences between the groups. Our findings provide support for the concept that the impaired function of mGluR5 underlies the symptoms of schizophrenia. They further supply a new perspective on the complex relationship between tobacco addiction and schizophrenia by identifying glutamatergic neurotransmission—in particularly mGluR5—as a possible connection to a shared vulnerability.
These joint practice guidelines, or procedure standards, were developed collaboratively by the European Association of Nuclear Medicine (EANM), the Society of Nuclear Medicine and Molecular Imaging ...(SNMMI), the European Association of Neurooncology (EANO), and the working group for Response Assessment in Neurooncology with PET (PET-RANO). Brain PET imaging is being increasingly used to supplement MRI in the clinical management of glioma. The aim of these standards/guidelines is to assist nuclear medicine practitioners in recommending, performing, interpreting and reporting the results of brain PET imaging in patients with glioma to achieve a high-quality imaging standard for PET using FDG and the radiolabelled amino acids MET, FET and FDOPA. This will help promote the appropriate use of PET imaging and contribute to evidence-based medicine that may improve the diagnostic impact of this technique in neurooncological practice. The present document replaces a former version of the guidelines published in 2006 (Vander Borght et al. Eur J Nucl Med Mol Imaging. 33:1374–80,
2006
), and supplements a recent evidence-based recommendation by the PET-RANO working group and EANO on the clinical use of PET imaging in patients with glioma (Albert et al. Neuro Oncol. 18:1199–208,
2016
). The information provided should be taken in the context of local conditions and regulations.
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