Advanced Imaging and Biopsy Techniques for Brain Tumor

(ReGIT Trial)

Overseen by Jason Parker, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Indiana University

Disqualifiers: Claustrophobia, Pacemaker, Pregnancy, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial uses advanced imaging techniques to take detailed pictures of brain tumors in patients with gliomas. Researchers aim to see if these images can predict genetic changes in the 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 data supports the effectiveness of this treatment for brain tumors?

Research shows that the use of O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET) in PET scans is effective in diagnosing and managing brain tumors by providing important information for tumor delineation and treatment planning. Additionally, combining [18F]FET PET with MRI improves the accuracy of identifying tumor boundaries, which is crucial for effective treatment. ^{1 2 3 4 5}

Are advanced imaging and biopsy techniques for brain tumors safe for humans?

Gadolinium-based contrast agents used in MRI for brain imaging are generally very safe, with mild side effects. However, there are concerns about rare risks like nephrogenic systemic fibrosis and gadolinium retention, especially in patients with kidney issues. ^{4 6 7 8 9}

How does the advanced imaging and biopsy technique treatment for brain tumors differ from other treatments?

This treatment is unique because it uses advanced imaging techniques like dynamic contrast-enhanced MRI to guide biopsies, which helps in selecting more accurate tissue samples for diagnosis compared to standard imaging methods. This approach improves the precision of biopsy targeting, especially in non-contrast-enhancing gliomas, leading to better diagnostic outcomes. ^{10 11 12 13 14}

Research Team

Jason Parker, PhD

Principal Investigator

Indiana University

Eligibility Criteria

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 am between 18 and 89 years old.

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

Trial Timeline

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

Treatment Details

Interventions

• Biopsy Collection (Procedure)
• CT scan (Imaging)
• FET F-18 (Radioisotope)
• MRI with gadolinium-based contrast (Imaging)
• O-15 Radioisotope (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.

Participant Groups

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+

Alan Palkowitz

Indiana University

Chief Executive Officer since 2020

PhD in Chemistry from Indiana University

David Ingram

Indiana University

Chief Medical Officer since 2020

MD from Indiana University School of Medicine

Children's Hospital of Philadelphia

Collaborator

Trials

749

Recruited

11,400,000+

Joseph W. St. Geme III

Children's Hospital of Philadelphia

Chief Medical Officer since 2021

MD, PhD, MPH

Madeline Bell

Children's Hospital of Philadelphia

Chief Executive Officer since 2015

BSc in Nursing from Villanova University, MSc in Organizational Dynamics from the University of Pennsylvania

Findings from Research

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]

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]

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]

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 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]

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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Current trends in the use of O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET) in neurooncology. [2021]

2. United States 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. [2020]

3. Germany 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. [2021]

4. France 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. [2022]

5. United States 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. [2016]

6. United States pubmed.ncbi.nlm.nih.gov

MR imaging advances in practice. [2019]

7. France 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. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Efficacy of gadoteridol for contrast-enhanced magnetic resonance imaging in children. [2015]

9. United States pubmed.ncbi.nlm.nih.gov

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

10. Austria pubmed.ncbi.nlm.nih.gov

Stereotactic indications for neuroradiological differential diagnosis. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Advanced Imaging for Biopsy Guidance in Primary Brain Tumors. [2020]

12. England pubmed.ncbi.nlm.nih.gov

Intra-individual comparison of ¹⁸F-FET and ¹⁸F-DOPA in PET imaging of recurrent brain tumors. [2022]

13. United States 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. [2019]

14. United States 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. [2016]