Diagnostic Assessment of Amino Acid PET/MRI in the Evaluation of Glioma and Brain Metastases

Study Overview
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Brief Summary
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MRI is used in clinical routine for diagnosing brain tumors, but has limitations in identifying tumor grade, true tumor extension and differentiate viable tumor tissue from treatment induced changes and recurrences. Amino acid PET has demonstrated a great potential for defining true tumor volume, differentiate viable tumor tissue from postoperative changes or radiation necrosis, selection of biopsy site, non-invasive grading of gliomas and for treatment planning and therapy response assessment. By combining PET with MRI, the diagnostic accuracy can improve significantly for these patients. More research is however needed to compare the most promising amino acid PET tracers in patients with glioma, but also to assess the diagnostic value of amino acid PET in patients with different brain metastases, where the knowledge concerning the uptake characteristics is limited. Three of the most promising amino acid tracers ([11C]-methyl-methionine (11C-MET), [18F] fluoro-ethyl-tyrosin (18F-FET) and anti-1-amino-3-[18F]fluorocyclobutane-1-carboxylic acid (18F-FACBC)) will be evaluated in 3 substudies in this project; WP1 Aminoacid PET/MRI in low and high grade glioma; WP2 Role of 11C-MET in high-grade glioma Gamma Knife® radiosurgery; and WP3 Amino acid PET in brain metastasis. The main aim of the study is to improve diagnostic accuracy, histopathological tissue sampling, delineation of tumor extent and therapy response assessment in gliomas and brain metastases with amino acid PET/MRI.

Official Title
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Diagnostic Assessment of Amino Acid PET/MRI in the Evaluation of Glioma and Brain Metastases

Conditions
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Brain Neoplasms

Intervention / Treatment
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* Other: Diagnostic Amino acid PET/MRI examination


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion criteria Glioma (LGG, HGG and recurrent HGG): Planned treatment for WHO grade II-IV diffuse glioma Adult patients (>18 years) Planned tissue sampling for histopathological diagnosis. KPS >60 (able to care for self) Inclusion criteria Brain Metastasis: Indication of surgery or stereotactic radiosurgery for 1-4 brain metastases Planned surgery: Suspicion of brain metastasis or known diagnosis Stereotactic surgery: Known primary cancer Adult patients (>18 years) Estimated survival at least 3 months after inclusion Exclusion Criteria: Exclusion criteria (Glioma and Brain Metastasis): Pacemakers or defibrillators not compatible with 3T MRI No ability to obtain informed consent (e.g. due to severe dysphasia or cognitive deficits). Pregnancy (pregnancy test for all women in fertile age when doubt about possible pregnancy exist) Breastfeeding Weight > 120 kg

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Glioma<br>20 low-grade (LGG) and 40 high-grade glioma (HGG) patients will be included from the Department of Neurosurgery at St. Olavs Hospital and the Department of Neurosurgery at the University hospital of North Norway and examined with 18F-FACBC PET/MRI at baseline and 4-6 months after surgery. Furthermore, 10 of the LGG patients and 10 of the HGG patients will be examined with an additional 18F-FET PET/MRI at baseline for comparison with 18F-FACBC. 30 recurrent HGG patients will be recruited from the Department of Neurosurgery and the Department of Oncology at the Haukeland University Hospital. These patients will be examined with 11C-MET PET/MRI at treatment/baseline and 1 month after radiosurgery. | Other: Diagnostic Amino acid PET/MRI examination<br>* Diagnostic Amino acid PET/MRI examination<br>|
| Brain Metastases<br>Patients with brain metastases (18F-FACBC: n=20, 18F-FET: n=20 and 11C-MET: n=30) will be included from the Department of Neurosurgery at St. Olavs Hospital, the Department of Neurosurgery at Haukeland University Hospital and the Department of Neurosurgery at the University hospital of North Norway, and examined with amino acid PET/MRI at baseline, 1 month after surgery/stereotactic radiosurgery (St. Olavs Hospital/UNN: Linac, Haukeland University Hospital: Gamma Knife® radiosurgery) and at suspicion of recurrence. | Other: Diagnostic Amino acid PET/MRI examination<br>* Diagnostic Amino acid PET/MRI examination<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnostic accuracy in detecting brain tumor tissue at baseline | Diagnostic accuracy, sensitivity, specificity, positive-and negative predictive values of PET, contrast-enhanced MRI (MRICE) and combined PET/MRI will be calculated by comparing images to histopathological results for the large non-localized biopsies as well as to the image-localized biopsies taken prior to resection. | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnostic accuracy using dynamic PET | Dynamic PET will be compared for differentiation between low-grade and high-grade tumors and to study the relationship between the time-activity-curve pattern and histology type. | Baseline | 
| Differentiation between recurrence and treatment related changes using PET/MRI | 18F-FACBC uptake (at follow-up), in terms of SUV, TBR, and TAC will be compared to MRI and baseline-PET to evaluate if PET can detect recurrent disease prior to MRI, or if PET can define early treatment response better than MRI. | 4-6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diagnosis, Magnetic Resonance Imaging, Positron-Emission Tomography, PET-tracer