Multiparametric Metabolic and Hypoxic PET/MRI Imaging for Brain Cancer

Overseen By Sebastian M Eady, BS

Age: Any Age

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Alabama at Birmingham

Must not be taking: Bevacizumab, Investigational drugs

Disqualifiers: Recurrent glioma, Pregnancy, Renal dysfunction, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new imaging method to better detect high-grade glioma, a type of brain cancer, in both children and adults. The goal is to determine if this approach can identify tumors after standard treatments like radiation. Participants will undergo a special PET/MRI scan using specific tracers, including O-(2-[18F]Fluoroethyl)-L-tyrosine (FET), to capture detailed images. Eligible participants have been diagnosed with high-grade glioma and have completed radiation therapy. The study aims to improve future monitoring and treatment of brain cancer. As an Early Phase 1 trial, this research focuses on understanding how the imaging method works in people, offering participants a chance to contribute to groundbreaking advancements in brain cancer detection.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you have used bevacizumab or an investigational drug within 3 months before the imaging study.

What prior data suggests that this imaging approach is safe for detecting high grade glioma?

Research has shown that O-(2-[18F]Fluoroethyl)-L-tyrosine (FET) is generally safe for patients. Studies have demonstrated that FET helps doctors see brain tumors more clearly. Many patients have used this imaging agent safely to diagnose brain tumors.

Although detailed safety data on side effects is limited, using FET in imaging has not raised major safety concerns. Since this trial is in an early phase, the main focus is on safety and patient tolerance. Doctors are closely monitoring for any side effects to ensure its safety.

In summary, FET has been used safely in many studies, and this early phase trial will help confirm its safety for future use. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores a new way of imaging brain cancer using a combination of PET/MRI scans with unique tracers, specifically FET and FMISO. Unlike standard imaging methods, this approach provides detailed insights into the tumor's metabolism and oxygen levels. This could lead to more precise treatment plans by showing how aggressive the tumor is and how it reacts to therapy. By improving how doctors visualize and understand brain tumors, this trial has the potential to significantly enhance patient care.

What evidence suggests that this imaging approach is effective for detecting high grade glioma?

In this trial, participants will undergo PET imaging using a special substance called FET. Research has shown that FET helps identify active brain tumor tissue. Studies have found that combining FET PET scans with MRI makes it much easier to detect cancerous tissue in people with brain tumors like gliomas. FET PET scans provide clearer images, simplifying the process of locating tumor cells. This method allows doctors to see the tumor more clearly, potentially leading to better treatment choices. Overall, evidence suggests that using FET PET/MRI is a promising way to effectively identify brain cancer tissue. ^{1 3 6 7 8}

Who Is on the Research Team?

Jonathan McConathy, MD, PhD

Principal Investigator

University of Alabama at Birmingham

Are You a Good Fit for This Trial?

This trial is for pediatric and adult patients with newly diagnosed high-grade gliomas who have completed standard radiation therapy. Participants must be 10 years or older, have a life expectancy over 12 weeks, and can undergo PET/MRI without anesthesia. Women of childbearing age need a negative pregnancy test. Exclusions include pregnancy, significant kidney issues, recurrent glioma, recent use of certain drugs like bevacizumab, or any condition that may hinder study completion.

Inclusion Criteria

I have a high-grade glioma and have received or am receiving radiation.

Females with childbearing potential must have a negative urine β-hCG test on the day of procedure or a serum beta-hCG test within 48 hours prior to the administration of FET or FMISO

I am at least 10 years old.

Exclusion Criteria

My kidney function is significantly impaired.

Inability to complete PET/MRI scans

My brain tumor has come back after treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

PET/MRI Imaging

Participants undergo FET and FMISO PET/MRI imaging to assess viable high grade glioma

2 weeks

2 visits (in-person)

Follow-up

Participants are monitored clinically and with standard of care brain MRI for progression-free survival (PFS) and overall survival (OS)

24 months

Regular visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• O-(2-[18F]Fluoroethyl)-L-tyrosine

Trial Overview The study tests a new imaging method using simultaneous PET/MRI with two tracers: FET to track amino acid transport and FMISO for hypoxia in tumors post-radiation therapy. The goal is to detect viable brain tumors after treatment and develop an automated workflow for future clinical trials and care standards.

How Is the Trial Designed?

Group I: PET imaging of system L amino acid transport with FET and hypoxia imaging with FMISO Experimental Treatment 1 Intervention

The participant will have a plastic peripheral intravenous (IV) catheter placed in the arm for Positron emission tomography (PET) tracer and MR contrast administration. FET O-(\[2-\[18F\]fluoroethyl)-L-tyrosine and FMISO 1H-1-(3-\[18F\]fluoro-2-hydroxypropyl)-2-nitroimidazole will be produced by the UAB Cyclotron PET Production Facility. PET/MRI will be performed using a GE Signa PET/MRI system in the AIF with specific imaging protocols for FET and FMISO studies. Upon completion of imaging, the peripheral IV catheter will be removed. The participant will be asked to urinate to reduce bladder dose after completion of each PET acquisition.Patients enrolled in the study will be followed clinically and with standard of care brain MRI. PFS and OS will be monitored for up to 24 months after completion of FET and FMISO PET/MRI studies.

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Published Research Related to This Trial

This study compared BOLD and TOLD MRI techniques with the radiotracer [18F]FMISO in tumor-bearing rats, revealing that both MRI methods can provide insights into tumor oxygenation and correlate with hypoxia levels indicated by PET imaging.

The findings suggest that regional variations in tumor oxygenation are important, as stronger correlations were found in well-perfused areas, highlighting the need for further research into the relationship between MRI signals and hypoxia in tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Examining correlations of oxygen sensitive MRI (BOLD/TOLD) with [18F]FMISO PET in rat prostate tumors. Zhou, H., Chiguru, S., Hallac, RR., et al.[2020]

In a study of 124 glioma patients, (18)F-FET PET demonstrated a higher diagnostic accuracy (93%) for detecting tumor progression or recurrence compared to conventional MRI (85%), particularly when specific uptake criteria were met.

The use of (18)F-FET PET not only improved sensitivity (93%) and specificity (100%) but also effectively distinguished between true tumor progression and treatment-related changes, making it a valuable tool in glioma management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of dynamic O-(2-18F-fluoroethyl)-l-tyrosine PET in the diagnosis of patients with progressive and recurrent glioma. Galldiks, N., Stoffels, G., Filss, C., et al.[2022]

In a study of 10 patients with recurrent high-grade glioma treated with bevacizumab/irinotecan, (18)F-FET PET identified 60% of patients as metabolic responders, while MRI only showed a complete response in 10% and partial response in 50%, indicating that (18)F-FET PET may be more sensitive in detecting treatment responses.

Responses detected by (18)F-FET PET were significantly associated with longer progression-free survival (9 months vs. 3 months) and overall survival (23 months vs. 3.5 months), suggesting that this imaging technique provides critical prognostic information that complements MRI assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Response assessment of bevacizumab in patients with recurrent malignant glioma using [18F]Fluoroethyl-L-tyrosine PET in comparison to MRI. Galldiks, N., Rapp, M., Stoffels, G., et al.[2022]

The newly developed 18F-labeled amino acid tracer, 18F-FET, shows high radiochemical purity (over 95%) and stability for at least 6 hours, indicating its safety for use in medical imaging.

In preclinical studies, 18F-FET demonstrated significantly lower uptake in normal brain tissues compared to tumors, providing clearer images of brain tumors than the commonly used 18F-FDG, suggesting its efficacy as a PET tracer for tumor imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Synthesis and preliminary studies of O-(2-[18F] fluoroethyl)-L-tyrosine as a positron emission tomography imaging agent]. Dang, YH., Wang, SZ., Cheng, X., et al.[2016]

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]

A new mathematical model has been developed to link anatomical MRI imaging with molecular PET imaging in glioblastoma multiforme (GBM), allowing for patient-specific virtual PET images that accurately reflect clinical scans.

This model incorporates factors like hypoxia and angiogenesis, providing insights into the tumor microenvironment and potentially improving our understanding of how these factors affect tracer activity and tumor behavior.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Applying a patient-specific bio-mathematical model of glioma growth to develop virtual [18F]-FMISO-PET images. Gu, S., Chakraborty, G., Champley, K., et al.[2021]

The study evaluated 393 patients and found that [(18)F]-fluoro-ethyl-l-tyrosine (18F-FET) PET has a high sensitivity of 87% for detecting high-grade brain tumors, indicating it is effective for identifying aggressive tumor types.

However, the specificity of 68% is limited due to tracer uptake in non-tumor brain lesions and disrupted blood-brain barriers, suggesting that while 18F-FET PET is useful, it may also yield false positives in certain conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[18F]-fluoro-ethyl-L-tyrosine PET: a valuable diagnostic tool in neuro-oncology, but not all that glitters is glioma. Hutterer, M., Nowosielski, M., Putzer, D., et al.[2021]

In a study of 98 patients with gadolinium-negative gliomas, dynamic 18F-FET PET imaging revealed distinct time activity curve (TAC) patterns that correlated with patient survival, with 5-year survival rates of 85% for increasing TACs, 47% for mixed TACs, and 19% for decreasing TACs.

The study found that TAC measurements serve as a strong independent biomarker for prognosis, regardless of tumor grade or IDH mutation status, highlighting their potential utility in guiding treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dynamic 18F-FET PET is a powerful imaging biomarker in gadolinium-negative gliomas. Kunz, M., Albert, NL., Unterrainer, M., et al.[2020]

The study involved 47 glioma patients and 63 lesions, demonstrating that combined 18F-fluorethyltyrosine (FET)-PET/MRI is effective in distinguishing between tumor recurrence and treatment-related changes, with a high area under the curve (AUC) of 0.89 for multiparametric analysis.

Static PET showed the highest sensitivity (80%) and specificity (85%) for identifying recurrence, while the multiparametric approach improved diagnostic accuracy, particularly when high specificity was required.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnosis of glioma recurrence using multiparametric dynamic 18F-fluoroethyl-tyrosine PET-MRI. Pyka, T., Hiob, D., Preibisch, C., et al.[2019]

Increasing tumor oxygenation using carbogen did not significantly change overall (18)F-FDG uptake in tumors, indicating that general tumor metabolism may remain stable under different oxygen conditions.

However, in the most hypoxic regions of the tumor, (18)F-FDG uptake showed a significant 21% reduction with increased oxygenation, suggesting that enhancing tumor oxygen levels could improve the accuracy of (18)F-FDG imaging by highlighting areas of lower glucose metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The influence of tumor oxygenation on (18)F-FDG (fluorine-18 deoxyglucose) uptake: a mouse study using positron emission tomography (PET). Chan, LW., Hapdey, S., English, S., et al.[2018]

The study found that O-(2-[18F]fluoroethyl)-l-tyrosine (18F-FET) is taken up significantly more by malignant thymoma cells compared to normal tissues, indicating its potential as a tumor imaging tracer.

In both mice and human studies, 18F-FET showed a clear biodistribution pattern, with tumor uptake being notably higher than in muscle tissue, suggesting its efficacy in distinguishing tumors from healthy organs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

O-(2-[18F]fluoroethyl)-L-tyrosine (18F-FET) uptake in mouse thymoma cells, and its biodistribution in mice and human volunteers. Abe, K., Hayashi, K., Sasaki, M., et al.[2016]

The study used dynamic [18F]FMISO PET imaging in mice and human patients to assess tumor hypoxic fractions (HFs), revealing that the method of quantification significantly affects the results, with HFs ranging from 2% to 85% depending on the metric used.

Tracer kinetic modeling (K i and k 3) showed a stronger correlation with direct oxygen measurements compared to tissue-to-blood ratios (TBR), suggesting it may enhance the reliability of hypoxia quantification in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantification of Tumor Hypoxic Fractions Using Positron Emission Tomography with [18F]Fluoromisonidazole ([18F]FMISO) Kinetic Analysis and Invasive Oxygen Measurements. Kelada, OJ., Rockwell, S., Zheng, MQ., et al.[2019]

L-[18F]FET is rapidly taken up by SW 707 colon carcinoma cells through the specific amino acid transport system L, demonstrating a significant accumulation factor of 3.0 to 5.0, while D-[18F]FET showed no accumulation.

In vivo studies in tumor-bearing mice revealed that L-[18F]FET has a half-life of 94 minutes in plasma and exhibits higher uptake in tumors compared to other organs, indicating its potential as an effective tracer for tumor imaging and therapy monitoring using PET.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigation of transport mechanism and uptake kinetics of O-(2-[18F]fluoroethyl)-L-tyrosine in vitro and in vivo. Heiss, P., Mayer, S., Herz, M., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/15689365/

O-(2-[18F]fluoroethyl)-L-tyrosine PET combined with MRI ... Combined use of MRI and FET PET in patients with cerebral gliomas significantly improves the identification of cellular glioma tissue and allows definite ...

2. academic.oup.com academic.oup.com/brain/article/128/3/678/693026

O-(2-[18F]fluoroethyl)-l-tyrosine PET combined with MRI ... Combined use of MRI and FET PET in patients with cerebral gliomas significantly improves the identification of cellular glioma tissue and allows definite ...

3. nature.com nature.com/articles/s41598-025-90472-8

An effective MRI perfusion threshold based workflow to ... While positron emission tomography with O-(2-[18F]fluoroethyl)-L-tyrosine) (18F-FET PET) offers higher diagnostic accuracy, its use is limited ...

4. jnm.snmjournals.org jnm.snmjournals.org/content/66/2/187

Borderline Findings in O-(2-[ 18 F]-Fluoroethyl)-l-Tyrosine ... The goal of this study was to investigate the frequency of borderline cases and the role of quantitative 18 F-FET PET parameters in this situation.

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0969805120300299

Current trends in the use of O-(2-[ 18 F]fluoroethyl)-L ... This review summarizes the basic knowledge about [ 18 F]FET and its clinical applications with a focus on more recent studies and discusses the future role of ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12196355/

Technology Transfer of O-(2-[18F] Fluoroethyl)-L-Tyrosine ... The diagnostic potential of O-(2-[18F] fluoroethyl)-L-tyrosine ([18F]FET) positron emission tomography (PET) has already been proven in many ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6917428/

Recurrent glioblastoma versus late posttreatment changes ... Recurrent glioblastoma versus late posttreatment changes: diagnostic accuracy of O-(2-[18F]fluoroethyl)-L-tyrosine positron emission tomography (18F-FET PET).

8. jnm.snmjournals.org jnm.snmjournals.org/content/53/2/207

Performance of 18 F-Fluoro-Ethyl-Tyrosine ( 18 F-FET) PET for ... The purpose of this systematic review and metaanalysis was to assess the diagnostic performance of 18 F-FET PET in patients with suspicion of PBT.