Glutamine PET Imaging for Colorectal Cancer

Overseen By Allison Cohen

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must be taking: Anti-EGFR mAb

Disqualifiers: Other malignancy, Previous EGFR therapy, others

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

Compensation: Varies

Number of Visits: 8

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new imaging methods to better detect tumors in people with metastatic colorectal cancer. Researchers compare two types of PET scans, using Carbon C 11 Glutamine and Fluorine F 18 L-glutamate Derivative BAY94-9392, to determine if they outperform standard MRI or CT scans. Individuals diagnosed with advanced colorectal cancer who have not undergone certain treatments may find this trial suitable. Participants will receive special imaging agents through an IV and have blood drawn during the scans. As a Phase 1 trial, the research focuses on understanding how these new imaging methods work in people, offering participants the chance to benefit from cutting-edge technology.

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

The trial protocol does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your doctor.

What prior data suggests that this imaging method is safe for detecting tumors in colorectal cancer patients?

Research has shown that both Carbon C 11 Glutamine and Fluorine F 18 L-glutamate Derivative BAY94-9392 are safe for humans. Studies indicate that PET imaging with 11C-glutamine is well tolerated by patients with advanced colorectal cancer, with no reported safety issues, and it aids doctors in visualizing cancer in various organs.

For Fluorine F 18 L-glutamate Derivative BAY94-9392, research suggests it is also well tolerated. Tests demonstrated that this imaging agent is absorbed effectively by tumors without causing problems for patients. Overall, these imaging methods have been safely used in studies to assist in cancer detection. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these imaging agents, Carbon C 11 Glutamine and Fluorine F 18 L-glutamate Derivative BAY94-9392, because they offer a new way to visualize colorectal cancer. Unlike standard imaging techniques that focus on tumor size or structure, these agents target metabolic activity, specifically how cancer cells use glutamine. This unique approach could help identify cancer more precisely and quickly, potentially improving diagnosis and monitoring of the disease.

What evidence suggests that this PET imaging method is effective for detecting tumors in metastatic colorectal cancer?

In this trial, participants will undergo PET imaging using both carbon C 11 glutamine and fluorine F 18 L-glutamate derivative BAY94-9392. Research has shown that carbon C 11 glutamine PET imaging effectively detects the spread of colorectal cancer, identifying whether the cancer has moved to organs like the lungs, brain, liver, and bones. This method is considered safe and provides a non-invasive way to locate cancerous areas.

Additionally, studies suggest that fluorine F 18 L-glutamate derivative BAY94-9392 can effectively image various cancers, including liver cancer, and has shown promise in detecting early responses to certain cancer treatments. This imaging method helps identify specific cancer activities, which is crucial for monitoring tumor growth. ^{1 2 4 6 7}

Who Is on the Research Team?

Simone Krebs

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with metastatic colorectal cancer that hasn't been treated with EGFR-directed therapy. They must have a tumor sample available, measurable disease by certain criteria, and be eligible for anti-EGFR antibody therapy. It's not for those who are pregnant, lactating, or have had another cancer in the past 5 years.

Inclusion Criteria

Ability to provide written informed consent in accordance with institutional policies

I have a tumor larger than 2 cm that can be measured by PET scan.

I have enough archived tissue from my primary colorectal cancer for gene analysis.

Exclusion Criteria

I have received treatment targeting EGFR before.

My weight is over 400 pounds or my body shape or disability prevents me from undergoing certain scans.

I have not had any other cancer in the last 5 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging

Participants receive 11C-glutamine and 18F-FSPG intravenously and undergo PET imaging over 120 minutes for each compound.

1-2 weeks

2 visits (in-person)

Treatment

Participants receive anti-EGFR mAb therapy in cycles, with imaging assessments every 8 weeks.

24 weeks

6 visits (in-person)

Follow-up

Participants are monitored for progression-free survival and overall survival.

Up to 4 years

What Are the Treatments Tested in This Trial?

Interventions

• Carbon C 11 Glutamine
• Fluorine F 18 L-glutamate Derivative BAY94-9392

Trial Overview The study tests how well two PET imaging agents (11C-glutamine and 18F-FSPG) detect tumors compared to standard MRI or CT scans in patients with metastatic colorectal cancer. The goal is to see if these new agents offer clearer images of the tumors.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 4 Interventions

Patients receive carbon C 11 Glutamine (11C-glutamine) IV and undergo PET imaging over 120 minutes. Beginning 2 hours to 7 days after 11C-glutamine PET, patients receive fluorine F 18 L-glutamate derivative BAY94-9392 (18F-FSPG) IV and also undergo PET imaging over 120 minutes. During each of the 11C-Glutamine and 18F-FSPG PET/CT scans, venous blood draws will be performed.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

The novel radiopharmaceutical 18F-FSPG shows excellent tumor visualization in both small animal models and human subjects with brain tumors, achieving a high tumor-to-brain ratio of 32.7, significantly better than other tracers like 18F-FDG and 18F-FET.

In a pilot study involving five human subjects, 18F-FSPG was well tolerated and effectively identified malignant lesions, indicating its potential as a reliable imaging agent for intracranial malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot Preclinical and Clinical Evaluation of (4S)-4-(3-[18F]Fluoropropyl)-L-Glutamate (18F-FSPG) for PET/CT Imaging of Intracranial Malignancies. Mittra, ES., Koglin, N., Mosci, C., et al.[2018]

The radiopharmaceutical 18F-FSPG demonstrated a high tumor detection rate in prostate cancer patients, with 89% detection on a per-patient basis and 87% on a per-lobe basis, indicating its potential effectiveness for imaging.

In patients with recurrent prostate cancer, 18F-FSPG PET showed good agreement with standard imaging methods in 78% of cases, suggesting it could be a reliable tool for assessing cancer recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Evaluation of (4S)-4-(3-[18F]Fluoropropyl)-L-glutamate (18F-FSPG) for PET/CT Imaging in Patients with Newly Diagnosed and Recurrent Prostate Cancer. Park, SY., Na, SJ., Kumar, M., et al.[2021]

The new tracer (18)F-FSPG demonstrated a high tumor detection rate in patients with hepatocellular carcinoma (HCC), successfully identifying tumors in all 5 patients studied, compared to only 3 out of 5 with the standard (18)F-FDG tracer.

(18)F-FSPG PET imaging was well tolerated by patients and showed strong tumor uptake with lower background noise from normal tissue, suggesting it may be a more effective option for visualizing HCC compared to (18)F-FDG.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

(4S)-4-(3-18F-fluoropropyl)-L-glutamate for imaging of xC transporter activity in hepatocellular carcinoma using PET: preclinical and exploratory clinical studies. Baek, S., Mueller, A., Lim, YS., et al.[2017]

(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 new PET tracer (18)F-FSPG shows promise for detecting malignant diseases, particularly in non-small cell lung cancer, with dosimetry estimates indicating a radiation dose of 9.5 mSv at a standard patient dose of 300 MBq, comparable to (18)F-FDG.

The absorbed dose to the urinary bladder wall was the highest, but this can be significantly reduced by encouraging patients to void their bladder frequently, lowering the effective dose to 4.5 mSv with a 0.75-hour voiding interval.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

(S)-4-(3-18F-fluoropropyl)-L-glutamic acid: an 18F-labeled tumor-specific probe for PET/CT imaging--dosimetry. Smolarz, K., Krause, BJ., Graner, FP., et al.[2016]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33931465/

First-in-Human PET Imaging and Estimated Radiation ... Conclusion: PET using 11C-glutamine appears safe for human use and allows noninvasive visualization of metastatic colon cancer lesions in multiple organs.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8717201/

Glutamine in Patients with Metastatic Colorectal Cancer Accumulation of 11C-glutamine was elevated and visualized in lung, brain, bone, and liver metastases, suggesting utility for cancer imaging. Conclusion: PET ...

3. auntminnie.com auntminnie.com/clinical-news/molecular-imaging/nuclear-medicine/article/15628349/carbon11-pet-tracer-appears-safe-for-colon-cancer-detection

Carbon-11 PET tracer appears safe for colon cancer ... PET imaging with a carbon-11 (C-11) glutamine radiotracer appears to be a safe and effective method for detecting metastatic colorectal cancer.

4. jnm.snmjournals.org jnm.snmjournals.org/content/jnumed/63/1/36.full.pdf

Glutamine in Patients with Metastatic Colorectal Cancer Accumulation of 11C-glutamine was elevated and visualized in lung, brain, bone, and liver metastases, suggesting utility for cancer imaging.

5. sciencedirect.com sciencedirect.com/science/article/pii/S2211383524003137

l-[5-11C]Glutamine PET imaging noninvasively tracks ... A novel [ 11 C]Gln PET imaging platform can noninvasively track glutaminolysis responses in NASH mice and assess metabolic therapy efficacy with BPTES.

6. biosignaling.biomedcentral.com biosignaling.biomedcentral.com/articles/10.1186/s12964-024-02018-6

Glutamine and cancer: metabolism, immune ... Glutaminase inhibitor CB-839 is now under clinical trials to evaluate safety and efficacy in combination with other anticancer drugs in cancers ...

7. nature.com nature.com/articles/s41598-025-20528-2

Glutaminase inhibitor CB-839 causes metabolic ... Colorectal cancer (CRC) cells are 'addicted' to glutamine to satisfy energy and biosynthetic needs. Inhibiting glutamine metabolism enzymes, ...