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

85 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing a new drug called F-Glutamine that helps find tumors using special scanners. It is aimed at patients who might have tumors. The drug is injected and tracked by the scanner to show where tumors might be. F-Glutamine has been evaluated for its safety in patients with metastatic colorectal cancer.

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.

Is F-Glutamine PET Imaging safe for humans?

In a study involving 25 adult cancer patients, F-Glutamine PET Imaging was found to be safe, as no adverse effects were reported after its use. ^{1 2 3 4 5}

How does F-Glutamine PET Imaging differ from other cancer imaging methods?

F-Glutamine PET Imaging is unique because it uses a special tracer that targets glutamine metabolism, which is often altered in aggressive tumors. This method can detect tumors that may not be visible with standard glucose-based imaging, providing a new way to identify and assess certain cancers. ^{1 2 3 4 5}

What data supports the effectiveness of the drug F-Glutamine for cancer imaging?

Research shows that F-Glutamine is effective in imaging tumors because it is taken up by cancer cells that grow and multiply quickly. It has been used successfully to detect various types of cancer, including breast, pancreas, and lung, by highlighting abnormal glutamine metabolism in these tumors. ^{1 2 3 4 6}

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

(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 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]

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]

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]

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

Comparative evaluation of 18F-labeled glutamic acid and glutamine as tumor metabolic imaging agents. [2022]

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

Alanine and glycine conjugates of (2S,4R)-4-[18F]fluoroglutamine for tumor imaging. [2019]

3. United States 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. [2023]

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

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

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

Synthesis of optically pure 4-fluoro-glutamines as potential metabolic imaging agents for tumors. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Automated synthesis of [(18)F](2S,4R)-4-fluoroglutamine on a GE TRACERlab™ FX-N Pro module. [2019]