Advanced Imaging and Biopsy Techniques for Brain Tumor

(ReGIT Trial)

Overseen By Mahsa Servati, MS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Indiana University

Disqualifiers: Claustrophobia, Pacemaker, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how brain tumors change over time and whether new imaging techniques, such as MRI and PET scans, can predict these changes. Participants will undergo advanced imaging and biopsies (procedures to collect small tissue samples) before their planned surgery. The goal is to improve understanding of tumor behavior and potentially guide future treatment strategies. Individuals diagnosed with certain types of brain tumors and planning surgery might be suitable candidates for this trial. As an unphased study, this trial offers participants the chance to contribute to groundbreaking research that could lead to better diagnostic tools and treatment options for brain tumors.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, since the study requires participants to be treatment-naïve for the brain tumor condition, it might imply that you should not be on any treatment for the tumor itself.

What prior data suggests that these advanced imaging and biopsy techniques are safe for brain tumor patients?

Research has shown that FET F-18, a type of PET scan, is generally easy for patients to handle. Studies have found that it helps doctors see brain tumors more clearly without causing serious side effects. Most people who undergo FET F-18 scans do not experience major problems.

For the O-15 radioisotope, used in another PET scan, research indicates it is also safe. This scan helps doctors understand brain blood flow and energy use. There are no significant reports of harm or discomfort for patients who have had O-15 scans.

Studies consider both FET F-18 and O-15 scans safe and well-tolerated by patients. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these advanced imaging and biopsy techniques for brain tumors because they offer a more precise way to understand and treat the disease. Unlike traditional imaging, this approach uses FET F-18 and O-15 radioisotopes in PET-CT scans, providing detailed insights into the tumor's metabolic activity. This could lead to better surgical planning and more targeted treatment strategies, potentially improving patient outcomes. Additionally, combining imaging with stereotactic core biopsy allows for more accurate tissue sampling, which is critical for personalized treatment plans. Overall, these techniques could significantly enhance the precision of brain tumor diagnosis and treatment.

What evidence suggests that these advanced imaging and biopsy techniques are effective for brain tumors?

In this trial, participants will undergo advanced imaging techniques to assess brain tumors. Research has shown that FET F-18 PET scans, which participants will receive, effectively diagnose brain tumors. They outperform FDG-PET scans, making them a preferred choice for identifying new brain tumors. High FET uptake ratios have appeared in patients with glioblastoma, indicating these scans effectively spot these tumors.

Additionally, the O-15 radioisotope, used in O-15 water PET scans, serves as another imaging tool in this trial to check blood flow in the brain. Studies have found that this method effectively shows how blood moves through brain tumors. Understanding blood flow is crucial because it can help predict how a tumor will behave and respond to treatment. Together, these imaging tools provide detailed information about brain tumors, aiding doctors in making informed decisions. ^{6 7 8 9 10}

Who Is on the Research Team?

Jason Parker, PhD

Principal Investigator

Indiana University

Are You a Good Fit for This Trial?

This trial is for adults aged 18-89 with a newly diagnosed Grade II-IV glioma brain tumor, who can lay still for imaging tests and are planning surgery to remove the tumor. They must be able to read/write in English and not have any conditions that prevent MRI scans.

Inclusion Criteria

Subject is able to read and write in English

I can lay on my back for up to 80 minutes.

My brain tumor is suspected or confirmed to be Grade II-IV glioma.

Exclusion Criteria

I have kidney issues and can't follow certain medication dosing due to my weight.

Subject has a medical contraindication to any element of the study procedures

Subject or their LAR has not read and signed the informed consent form, or does not understand its contents

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Imaging and Biopsy

Subjects undergo PET-CT scans, MRI, and blood draws at the baseline visit, followed by a biopsy visit with MRI and biopsy sample collection.

2 visits

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up MRIs and other scans as part of regular care.

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Biopsy Collection
• CT scan
• FET F-18
• MRI with gadolinium-based contrast
• O-15 Radioisotope

Trial Overview

The study examines how brain tumors change over time using advanced imaging techniques like MRI/PET scans combined with biopsies. It aims to see if these tools can predict genetic mutations in the tumors.

How Is the Trial Designed?

Group I: Baseline Imaging and Biopsy Experimental Treatment 5 Interventions

Subjects will receive a PET-CT with the radiopharmaceuticals FET and O-15 Water (under RDRC approval for basic research) prior to their standard of care neurosurgery via stereotactic core biopsy. Research samples will be collected for analysis intraoperatively.

Who Is Running the Clinical Trial?

Indiana University

Lead Sponsor

Trials

1,063

Recruited

1,182,000+

Children's Hospital of Philadelphia

Collaborator

Trials

749

Recruited

11,400,000+

Published Research Related to This Trial

In a study involving 20 patients with suspected brain tumors, (18)F-FET PET showed significantly better tumor-to-brain contrast and anatomical structure discrimination compared to (123)I-IMT SPECT, suggesting it may be a more effective imaging method for brain tumors.

Both imaging techniques demonstrated a strong correlation in tumor uptake, indicating that experiences with (123)I-IMT SPECT could be applicable to (18)F-FET PET, but (18)F-FET PET's superior performance highlights its potential for improved diagnostic accuracy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of O-(2-18F-fluoroethyl)-L-tyrosine PET and 3-123I-iodo-alpha-methyl-L-tyrosine SPECT in brain tumors. Pauleit, D., Floeth, F., Tellmann, L., et al.[2016]

Using Ktrans maps from dynamic contrast-enhanced MRI (DCE-MRI) for biopsy target selection in glioma patients resulted in more accurate tissue samples compared to traditional imaging methods, with significant improvements noted in non-contrast-enhancing gliomas.

In a study of 28 patients, Ktrans-based samples showed higher diagnostic concordance with gross tumor diagnoses, particularly in non-contrast-enhancing gliomas, suggesting that Ktrans can enhance biopsy planning and improve diagnostic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biopsy targeting with dynamic contrast-enhanced versus standard neuronavigation MRI in glioma: a prospective double-blinded evaluation of selection benefits. Keil, VC., Pintea, B., Gielen, GH., et al.[2019]

In a study of 56 glioma patients, O-(2-(18)F-fluoroethyl)-L-tyrosine ((18)F-FET) PET imaging provided significantly higher tumor-to-brain ratios (TBR) and larger tumor volumes compared to perfusion-weighted MR imaging (PWI), indicating its superior ability to detect metabolically active tumor tissue.

The spatial congruence between (18)F-FET PET and rCBV maps was poor, suggesting that these imaging techniques provide different and complementary information about brain tumors, particularly in gliomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of 18F-FET PET and perfusion-weighted MR imaging: a PET/MR imaging hybrid study in patients with brain tumors. Filss, CP., Galldiks, N., Stoffels, G., et al.[2016]

Gadolinium contrast agents, including gadopentetate dimeglumine, gadodiamide, and gadoteridol, significantly enhance the diagnostic capabilities of MRI for brain and spine imaging, providing critical information that helps confirm or rule out conditions.

These agents are extremely safe and well-tolerated, with generally mild side effects, making them a reliable choice in clinical practice for improving diagnostic confidence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MR imaging advances in practice. Drayer, BP.[2019]

PET imaging with the amino acid analogue [18F]FET has proven effective in brain tumor diagnostics, providing critical information for tumor delineation, therapy planning, and monitoring treatment responses.

[18F]FET shows low accumulation in benign lesions and healthy brain tissue, allowing for clear differentiation between tumor and non-tumor areas, which has led to its preference over shorter-lived tracers like [11C]MET in many Western European medical centers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current trends in the use of O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET) in neurooncology. Stegmayr, C., Stoffels, G., Filß, C., et al.[2021]

Modern imaging techniques like MRI, CT scans, and angiography are excellent for locating brain tumors but do not provide enough detail about the specific type of tumor, making biopsies essential for accurate diagnosis.

Stereotactic biopsy, which uses small twist-drill burr holes, offers a less invasive option for obtaining tissue samples from potentially inoperable brain lesions, allowing for precise diagnosis while minimizing patient risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic indications for neuroradiological differential diagnosis. Balériaux, D., Parizel, PM., Matos, C., et al.[2019]

In a study of 460 patients undergoing contrast-enhanced MRI, gadoteridol demonstrated safety and good image quality comparable to other macrocyclic gadolinium-based contrast agents, with only 1.09% experiencing adverse events.

The diagnostic accuracy for identifying malignancy was high for both gadoteridol (95.4%) and other agents (96.9%), showing no significant differences, indicating that gadoteridol is an effective option for CNS imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnostic efficacy and safety of gadoteridol compared to gadobutrol and gadoteric acid in a large sample of CNS MRI studies at 1.5T. Del Poggio, A., Anello, G., Calloni, SF., et al.[2022]

In a study of 35 patients with newly diagnosed grade II or III gliomas, those with PET-positive tumors showed significantly higher amino acid uptake, indicating a more aggressive tumor biology.

Patients with PET-negative lesions had a significantly longer progression-free survival compared to those with PET-positive gliomas, suggesting that [18F]FET-PET/CT imaging can provide valuable prognostic information beyond traditional clinical and molecular markers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic Value of O-(2-[18F]Fluoroethyl)-L-Tyrosine PET/CT in Newly Diagnosed WHO 2016 Grade II and III Glioma. Kertels, O., Kessler, AF., Mihovilovic, MI., et al.[2020]

Advanced MR-based perfusion and spectroscopy techniques can enhance the accuracy of glioma sampling by identifying areas of highest tumor grade for biopsy, which is crucial for diagnosis and clinical trial eligibility.

In a reported case of a patient with gliomatosis cerebri, the integration of these advanced imaging methods with conventional MR successfully guided a diagnostic biopsy, demonstrating their practical application in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advanced Imaging for Biopsy Guidance in Primary Brain Tumors. Moussazadeh, N., Tsiouris, AJ., Ramakrishna, R.[2020]

Gadolinium-based contrast agents (GBCAs) are generally safe for use in MRI, but concerns have emerged regarding nephrogenic systemic fibrosis and gadolinium retention in the body.

Recent advancements in MRI technology allow for many procedures to be performed without GBCAs, particularly in patients with chronic conditions, leading to updated MRI protocols that enhance safety and standardize practices in neuroradiology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Consensus Guidelines of the French Society of Neuroradiology (SFNR) on the use of Gadolinium-Based Contrast agents (GBCAs) and related MRI protocols in Neuroradiology. Lersy, F., Boulouis, G., Clément, O., et al.[2021]

In a multicenter clinical trial involving 101 children, gadoteridol significantly improved the detection and characterization of brain and spine pathologies during MRI, with unblinded readers noting enhancement in 70% of brain cases compared to 50-67% by blinded readers.

The use of gadoteridol provided additional diagnostic information in 82% of brain studies and 63% of spine studies, indicating its efficacy in potentially changing patient diagnoses and improving clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of gadoteridol for contrast-enhanced magnetic resonance imaging in children. Ball, WS., Parker, JR., Davis, PC., et al.[2015]

In a study of 766 patients undergoing contrast-enhanced MRI, Clariscan (gadoterate meglumine) and other gadolinium-based contrast agents significantly increased diagnostic confidence in 95% of cases and led to a change in radiological diagnosis for 65% of patients.

Clariscan demonstrated an excellent safety profile, with no adverse events reported, and was associated with high image quality ratings in 94% of patients, indicating its effectiveness for CNS imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gadolinium-based contrast agents for imaging of the central nervous system: A multicenter European prospective study. Heshmatzadeh Behzadi, A., McDonald, J.[2022]

In a study involving 16 patients with recurrent low-grade astrocytoma and high-grade glioblastoma, (18)F-DOPA showed superior tumor-to-brain and tumor-to-blood ratios compared to (18)F-FET, indicating better imaging contrast for brain tumors outside the striatum.

While (18)F-DOPA provided better contrast ratios, (18)F-FET offered valuable insights into tumor grading and had lower uptake in the striatum, suggesting that both tracers have unique advantages depending on the imaging context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intra-individual comparison of ¹⁸F-FET and ¹⁸F-DOPA in PET imaging of recurrent brain tumors. Kratochwil, C., Combs, SE., Leotta, K., et al.[2022]

In a study of 33 patients with glioma, O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) PET imaging identified significantly larger tumor volumes compared to contrast-enhanced MRI, with average volumes of 77.84 cm³ versus 34.59 cm³, respectively.

Histopathological analysis confirmed that all biopsy samples from areas with increased FET uptake were glioma tissue, while only 13 out of 21 samples showed enhancement on CE MRI, highlighting the importance of combining FET-PET and CE MRI for accurate tumor delineation in treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simultaneous FET-PET and contrast-enhanced MRI based on hybrid PET/MR improves delineation of tumor spatial biodistribution in gliomas: a biopsy validation study. Song, S., Cheng, Y., Ma, J., et al.[2021]

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Evaluation of O-(2-[18F]-Fluoroethyl)-L-Tyrosine in the ...

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