F-Glutamine PET Imaging for Cancer

Overseen By Mark Dunphy, D.O.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Breast-feeding, Claustrophobia, Hepatic issues, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new experimental drug called F-Glutamine to determine if it can help doctors find tumors using PET scans. Researchers inject the drug in small amounts to observe its movement in the body and its duration in the blood. They hope F-Glutamine will improve tumor detection compared to standard scans. This trial may suit individuals with a confirmed solid tumor or lymphoma who are interested in new diagnostic methods. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new diagnostic drug.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study doctors to get a clear answer.

What prior data suggests that F-Glutamine is safe for use in humans?

Research has shown that using 18F-Fluoroglutamine, or F-Glutamine, in animals has been promising. In these studies, tumors absorbed F-Glutamine, suggesting it could help detect tumors. However, this trial marks the first time F-Glutamine is tested in humans. As an early-stage trial, the main focus is on safety.

In this study, researchers will inject only a tiny amount of F-Glutamine into participants to observe its behavior in the body. Since this is the first human trial, no specific safety data from previous human use exists. However, the trial is designed with caution, ensuring careful monitoring to quickly identify any side effects. Participants can feel reassured that the small amount used minimizes potential risks. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the F-Glutamine PET Imaging technique because it offers a new way to visualize cancer metabolism in the body. Unlike traditional imaging methods that often rely on glucose metabolism, this trial uses [18F] 4-L-Fluoroglutamine, which targets a different pathway by focusing on glutamine uptake in cancer cells. This can potentially provide more precise information about tumor activity and might help in diagnosing and monitoring cancer more effectively. By providing this novel insight, it could lead to better personalized treatment plans for patients.

What evidence suggests that F-Glutamine PET imaging is effective for detecting tumors?

This trial evaluates the use of 18F-4-L-Fluoroglutamine (F-Glutamine) as a promising tool for imaging tumors. Research indicates that tumor cells absorb and retain F-Glutamine, making it useful for cancer detection. Animal studies have shown consistent results across different tests. This imaging method targets how cancer cells use glutamine for energy. By highlighting areas with increased glutamine activity, F-Glutamine PET scans could identify tumors more effectively than some standard imaging methods. Although this trial is in the early stages of testing in humans, initial findings suggest promise for its role in cancer detection. ^{1 5 6 7 8}

Who Is on the Research Team?

Mark Dunphy, DO

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults aged 21-90 with confirmed solid tumors or lymphoma, which can be measured or evaluated. Women of childbearing age must have a negative pregnancy test and avoid unprotected sex during the study. Participants cannot join if they refuse IV lines, are breastfeeding, can't tolerate scans (like due to claustrophobia), have certain liver/renal conditions, or an acute major illness.

Inclusion Criteria

Negative serum pregnancy test for female patients of childbearing age and potential (as defined by MSKCC Standards & Guidelines), from assays obtained <2 weeks prior to study enrollment. Patients will be advised against having unprotected sexual intercourse from the time of the negative serum pregnancy test until after completing their participation in the study.

I have a confirmed cancer diagnosis and it can be measured for treatment response.

I am between 21 and 90 years old.

Exclusion Criteria

My kidney function is below normal based on recent tests.

Breast-feeding

Albumin < 3 g/dl

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a microdose of [18F] 4-L-Fluoroglutamine (2S,4R) and undergo PET imaging to evaluate pharmacokinetics, metabolism, and biodistribution

1 day

Multiple time points during one day

Optional Repeat Treatment

Eligible patients can optionally participate in the study a second time, receiving another microdose and undergoing the same evaluations

1 day

Multiple time points during one day

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• [18F] 4-L-Fluoroglutamine (2S,4R)

Trial Overview [18F] 4-L-Fluoroglutamine (F-Glutamine) is being tested in this Phase I trial. It's a new drug used with PET scanners to detect where it travels in the body after injection. The goal is to see how long F-Glutamine stays in the blood and its distribution as a potential way to find tumors more effectively than current methods.

How Is the Trial Designed?

Group I: [18F] 4-L-Fluoroglutamine (2S,4R) Experimental Treatment 1 Intervention

This pilot, first in-human microdose PET trial of the positron-emitting agent \[18F\] 4-L-Fluoroglutamine (2S,4R) will be an open-label study. The \[18F\] 4-L-Fluoroglutamine (2S,4R) agent will be administered by bolus intravenous injection. In all study patients, the pharmacokinetics, metabolism, and biodistribution of \[18F\] 4-L-Fluoroglutamine (2S,4R) will be evaluated by non-invasive blood- and PET-based assays, at multiple time points (see Table 1,) during one day. Eligible patients optionally can participate in the study twice, on a separate date, receiving a second radiotracer microdose of \[18F\] 4-L-Fluoroglutamine (2S,4R), followed by non-invasive blood- and PET-based assays. At the discretion of the investigator, scan 3 can be waived.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Published Research Related to This Trial

The newly developed dipeptides [18F]Gly-4F-Gln and [18F]Ala-4F-Gln rapidly convert to the active imaging agent (2S,4R)-4-[18F]fluoroglutamine in the bloodstream, indicating their potential as effective prodrugs for tumor imaging.

Both dipeptides showed rapid localization in tumor tissues during PET imaging in rat models, with [18F]Ala-4F-Gln being particularly promising for imaging glutaminolysis in tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Alanine and glycine conjugates of (2S,4R)-4-[18F]fluoroglutamine for tumor imaging. Zha, Z., Ploessl, K., Lieberman, BP., et al.[2019]

The novel PET reporter [18F]FGln showed significantly higher uptake in clear cell renal cell carcinoma (ccRCC) cells and lung lesions compared to normal kidney cells and lung tissue, indicating its potential for improved detection and assessment of ccRCC.

The uptake of [18F]FGln was influenced by factors such as glutamine availability and the activity of the ASCT2 transporter, but treatment with the glutaminase inhibitor CB-839 did not alter [18F]FGln retention in ccRCC tumors, suggesting complex interactions in tumor metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PET/MR Imaging of a Lung Metastasis Model of Clear Cell Renal Cell Carcinoma with (2S,4R)-4-[18F]Fluoroglutamine. Pollard, AC., Paolillo, V., Radaram, B., et al.[2023]

A new method was developed to synthesize all four stereoisomers of 4-fluoro-glutamines with high yields and optical purity, which is important for creating effective imaging agents.

Preliminary studies showed that these fluorine-18 labeled 4-fluoroglutamines could be used for PET imaging of tumors that rely on glutamine for energy, indicating their potential as diagnostic tools in cancer detection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis of optically pure 4-fluoro-glutamines as potential metabolic imaging agents for tumors. Qu, W., Zha, Z., Ploessl, K., et al.[2022]

In a study involving 25 adult cancer patients, the radiologic imaging agent fluorine 18-(2S,4R)-4-fluoroglutamine (FGln) was safely administered with no adverse effects, demonstrating its potential as a tumor imaging agent.

FGln PET scans successfully identified tumors in 17 out of 25 patients, particularly in aggressive cancers with mutations affecting glutamine metabolism, suggesting that FGln could serve as a valuable biomarker for targeted imaging in various cancer types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In Vivo PET Assay of Tumor Glutamine Flux and Metabolism: In-Human Trial of 18F-(2S,4R)-4-Fluoroglutamine. Dunphy, MPS., Harding, JJ., Venneti, S., et al.[2019]

(18)F-labeled (2S,4R)-4-fluoro-l-glutamine (4F-GLN) shows higher uptake in tumor cells compared to (18)F-labeled (2S,4R)-4-fluoro-l-glutamate (4F-GLU), making it a more effective imaging agent for tumors.

In vivo studies indicate that (18)F-4F-GLN has prolonged retention in tumors due to its incorporation into proteins, while (18)F-4F-GLU remains mostly as a free amino acid, suggesting different metabolic pathways for these tracers in tumor imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative evaluation of 18F-labeled glutamic acid and glutamine as tumor metabolic imaging agents. Ploessl, K., Wang, L., Lieberman, BP., et al.[2022]

The automated synthesis of [(18)F]FGln, a potential imaging agent for tumor diagnosis, was successfully achieved in about 80 minutes with a radiochemical yield of 21%, indicating its feasibility for clinical use.

With a radiochemical purity of over 98% and good reproducibility, [(18)F]FGln shows promise for improving PET imaging, particularly for tumors that do not show up on standard [(18)F]FDG scans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Automated synthesis of [(18)F](2S,4R)-4-fluoroglutamine on a GE TRACERlab™ FX-N Pro module. Zhang, X., Basuli, F., Shi, ZD., et al.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39787098/

Reproducibility and repeatability of 18F-(2S, 4R) 18F-Gln is a PET tracer designed for imaging glutamine uptake and metabolism. This study illustrates high reproducibility and repeatability with 18F-Gln for in ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT03568799

4-[18F]Fluoroglutamine PET/CT in Imaging Patients With ... This clinical trial studies positron emission tomography (PET) imaging utilizing 18F-(2S,4R)4-fluoroglutamine, a glutamic acid derivative, to image patients ...

3. jnm.snmjournals.org jnm.snmjournals.org/content/52/12/1947

PET Imaging of Glutaminolysis in Tumors by 18F-(2S,4R)4 ... 18 F-(2S,4R)4-fluoroglutamine is selectively taken up and trapped by tumor cells. It may be useful as a novel metabolic tracer for tumor imaging.

4. journals.plos.org journals.plos.org/plosone/article?id=10.1371/journal.pone.0313123

4-fluoroglutamine PET imaging in preclinical oncology models 18 F-Gln is a PET tracer designed for imaging glutamine uptake and metabolism. This study illustrates high reproducibility and repeatability with 18 F-Gln for ...

5. dctd.cancer.gov dctd.cancer.gov/drug-discovery-development/reagents-materials/imaging-ind-resources/documentation/18f-glutamine-ib.pdf

Investigator's Brochure [18F] 4-L-Glutamine (2S,4R) Glutamine is the most abundant free amino acid in the blood, whose circulating concentration is around 0.5 mmol/L. Despite being a nonessential amino acid, ...

6. aacrjournals.org aacrjournals.org/cancerres/article/77/6/1476/624892/18F-2S-4R-4-Fluoroglutamine-PET-Detects-Glutamine

[18F](2S,4R)4-Fluoroglutamine PET Detects Glutamine Pool ... These findings reveal the utility of a noninvasive PET imaging method to monitor pharmacodynamic responses to cancer drugs that target glutamine breakdown.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03568799

4-[18F]Fluoroglutamine PET/CT in Imaging Patients With ... This clinical trial studies positron emission tomography (PET) imaging utilizing 18F-(2S,4R)4-fluoroglutamine, a glutamic acid derivative, to image patients ...

8. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK83582/

18F-(2S,4R)4-fluoroglutamine - NCBI - NIH Lieberman et al. studied the biodistribution of [ 18 F]4-FGln in normal mice and rats and in mice and rats bearing xenograft tumors.