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

6 Participants Needed

Trial Summary

What is the purpose of this trial?

The clinical trial studies how well 11C-glutamine and 18F-FSPG positron emission tomography (PET) imaging works in detecting tumors in patients with metastatic colorectal cancer compared to standard imaging methods such as magnetic resonance imaging (MRI) or computed tomography (CT) scanning.

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 data supports the effectiveness of the drug used in the Glutamine PET Imaging for Colorectal Cancer trial?

Research shows that the drug 18F-FSPG, used in PET imaging, can help detect changes in tumors early in colorectal cancer, especially when combined with other treatments. It has also shown promise in imaging other cancers, like prostate and lung cancer, by highlighting abnormal glutamine metabolism, which is often present in aggressive tumors. ^{1 2 3 4 5}

Is 18F-FSPG safe for use in humans?

Pilot studies with 18F-FSPG in healthy volunteers and patients with various cancers showed promising results, with low background uptake in major organs, suggesting it is generally safe for human use. ^{1 3 4 6 7}

How does the drug used in Glutamine PET Imaging for Colorectal Cancer differ from other treatments?

The drug used in Glutamine PET Imaging for Colorectal Cancer, known as (18)F-FSPG, is unique because it is a radiopharmaceutical that allows for non-invasive imaging of tumors by targeting glutamine metabolism, which is often altered in cancer cells. This approach is different from traditional treatments as it provides a way to assess early response to therapies targeting specific cancer pathways, such as EGFR and glutaminolysis, without directly treating the cancer itself. ^{2 3 5 6 8}

Research Team

Lesley Flynt, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

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

Ability to provide written informed consent in accordance with institutional policies

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

(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]

References

1. United States 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. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Feasibility of [18F]FSPG PET for Early Response Assessment to Combined Blockade of EGFR and Glutamine Metabolism in Wild-Type KRAS Colorectal Cancer. [2023]

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

(S)-4-(3-18F-fluoropropyl)-L-glutamic acid: an 18F-labeled tumor-specific probe for PET/CT imaging--dosimetry. [2016]

4. United States 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. [2017]

5. 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]

6. United States 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. [2018]

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

Simplified and Highly-reliable automated production of [18F]FSPG for clinical studies. [2023]

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

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