F-Tryptophan PET/CT Imaging for Cancer

Overseen By Csaba Juhasz, M.D., Ph.D

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Barbara Ann Karmanos Cancer Institute

Must be taking: Somatostatin analogs

Must not be taking: Targeted agents, Cytotoxic chemotherapy

Disqualifiers: Pregnancy, Severe intracranial pressure, others

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

Compensation: Varies

Number of Visits: 1

24 Participants Needed

Trial Summary

What is the purpose of this trial?

Imaging procedures such as 1-(2-\[18F\]FLUOROETHYL)-L-Tryptophan PET/CT in patients with cancers may help doctors assess a patient's response to treatment and help plan the best treatment in the future. The purpose is to see if there can be a better differentiation of tumor and non-tumor tissue where the tumor tissue has a higher uptake of Tryptophan.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on certain treatments like targeted agents, cytotoxic chemotherapy, or telotristat ethyl, you may need to stop them before participating.

What data supports the effectiveness of the drug 1-(2-[18F]FLUOROETHYL)-L-Tryptophan for cancer imaging?

Research shows that F-18-labeled tryptophan-based radiotracers, like 1-(2-[18F]fluoroethyl)-L-tryptophan, are promising for cancer imaging because they accumulate in tumor cells and have favorable tumor-to-background ratios compared to other tracers. These tracers are taken up by cancer cells through specific transport mechanisms, making them effective for imaging tumors. ^{1 2 3 4 5}

Is F-Tryptophan PET/CT Imaging for Cancer safe for humans?

The studies on F-Tryptophan PET/CT imaging agents, like 7-[18F]Fluorotryptophan, show that they are stable and have been used in animal models without reported safety issues, suggesting they may be safe for human use, but specific human safety data is not detailed in these studies. ^{2 5 6 7 8}

How does F-Tryptophan PET/CT Imaging for Cancer differ from other cancer imaging drugs?

F-Tryptophan PET/CT Imaging uses a special type of imaging agent that targets tryptophan metabolism, which is different from traditional imaging agents that often target glucose metabolism. This approach can help distinguish cancerous tissues from inflamed tissues, providing clearer images for cancer diagnosis. ^{1 2 4 5 9}

Research Team

Csaba Juhasz, M.D.,Ph.D

Principal Investigator

Barbara Ann Karmanos Cancer Institute

Eligibility Criteria

Adults over 18 with certain cancers (brain, breast, neuroendocrine, colorectal) and visible tumors at least 1cm in diameter. Participants must be able to undergo a PET/CT scan for 70 minutes and not be pregnant or breastfeeding. They should have an ECOG performance status of ≤2 and meet specific criteria based on their cancer type.

Inclusion Criteria

My cancer is a well-differentiated neuroendocrine tumor that has spread.

Patients must sign an informed consent indicating that they are aware of the investigational nature of this study

Targeted lesion (tumor) is at least 1 cm in diameter as shown by clinical imaging

Exclusion Criteria

I am currently on medication specifically for my cancer.

Patients who are pregnant or lactating are excluded

I had tumor surgery or radiation less than a month before my PET scan.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging Procedure

Participants undergo 1-(2-[18F]Fluoroethyl)-L-Tryptophan PET/CT imaging to assess tracer uptake in tumor and non-tumor tissues

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging procedure

4 weeks

Treatment Details

Interventions

• 1-(2-[18F]FLUOROETHYL)-L-Tryptophan

Trial Overview The trial is testing the effectiveness of a new imaging procedure using F-Tryptophan PET/CT to distinguish between tumor tissue and non-tumor tissue in various cancers. The goal is to improve treatment planning by better identifying how tumors take up Tryptophan.

Participant Groups

Group I: [18F]FETrp PET radiotracer Experimental Treatment 1 Intervention

All participants will receive the tracer to evaluate the uptake of \[18F\]FETrp PET/CT on intra- and extracranial cancers.

Who Is Running the Clinical Trial?

Barbara Ann Karmanos Cancer Institute

Lead Sponsor

Trials

166

Recruited

9,300+

Washington University School of Medicine

Collaborator

Trials

2,027

Recruited

2,353,000+

Findings from Research

The new amino acid tracer [(18)F]-L-FPTP was developed with a high radiochemical purity of over 99% and a yield of 21.1%, making it a promising candidate for PET imaging in cancer diagnosis.

[(18)F]-L-FPTP demonstrated superior ability to differentiate tumors from inflammation compared to traditional tracers like [(18)F]FDG, showing a tumor-to-inflammation uptake ratio of 2.53, indicating its potential for more accurate cancer imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiosynthesis and biological evaluation of 5-(3-[18F]fluoropropyloxy)-L-tryptophan for tumor PET imaging. He, S., Tang, G., Hu, K., et al.[2016]

Two new fluorine-18 labeled tryptophan analogs, [(18)F]2-FPTRP and [(18)F]5-FPTRP, were developed for tumor imaging using PET, showing high radiochemical purity and effective synthesis yields of 29-34%.

In vivo studies demonstrated that [(18)F]2-FPTRP effectively accumulates in small cell lung cancer cells via large neutral amino acid transporters, achieving high tumor/background ratios comparable to established imaging agents, indicating its potential as a reliable radiotracer for cancer detection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and biological evaluation of ¹⁸F-labeled fluoropropyl tryptophan analogs as potential PET probes for tumor imaging. Chiotellis, A., Mu, L., Müller, A., et al.[2015]

The new tumor probe [C]-L-CMTP shows high uptake in tumor tissues, particularly in S180 fibrosarcoma and lung tumors, indicating its potential as an effective PET imaging agent for tumors.

[C]-L-CMTP is primarily transported by the amino acid transport systems B and LAT1, and it does not incorporate into proteins, which may enhance its specificity for tumor imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical evaluation of 5-([11C]-methyloxy)-L-tryptophan as a potential PET molecular imaging probe. He, S., Tang, G., Hu, K., et al.[2019]

A systematic review of 19 studies identified 15 unique F-18-labeled tryptophan derivative PET radiotracers, which show promise for tumor imaging due to their ability to accumulate in tumor cells and favorable tumor-to-background ratios.

Key enzymes in the kynurenine pathway, such as IDO and TDO, are targeted by several of these tracers, indicating their potential role in imaging tumor immune resistance and aiding in the understanding of cancer biology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluorine-18-Labeled PET Radiotracers for Imaging Tryptophan Uptake and Metabolism: a Systematic Review. John, F., Muzik, O., Mittal, S., et al.[2021]

Three new fluoroethoxy tryptophan analogues were developed for tumor imaging, with [(18)F]6-FEHTP showing the best tumor/background ratio in PET imaging of xenograft-bearing mice, outperforming other tracers and the established tyrosine analogue [(18)F]l-FET.

The uptake mechanism of [(18)F]6-FEHTP in small cell lung cancer cells suggests it is primarily transported via large neutral amino acid transporters, indicating a specific pathway for tumor targeting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and biological evaluation of (18)F-labeled Fluoroethoxy tryptophan analogues as potential PET tumor imaging agents. Chiotellis, A., Muller, A., Mu, L., et al.[2020]

A new method for creating fluorotryptophans labeled with 18F has been developed, resulting in high cellular uptake in various tumor cell lines, which could help in detecting different diseases like cancer and neurological disorders.

Among the different fluorotryptophans tested, 7-[18F]FTrp showed excellent stability in vivo and effectively highlighted serotonergic areas in the brain, making it a promising PET probe for imaging tryptophan metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Discovery of 7-[18F]Fluorotryptophan as a Novel Positron Emission Tomography (PET) Probe for the Visualization of Tryptophan Metabolism in Vivo. Zlatopolskiy, BD., Zischler, J., Schäfer, D., et al.[2019]

A new tryptophan analog, l-5-(2-[(18)F]fluoroethoxy)-tryptophan (5-(18)FEHTP), can be synthesized remotely with a radiochemical yield of 12-16% in just 65 minutes and has a high purity of over 98%.

In mouse studies, 5-(18)FEHTP showed significant uptake in tumors, suggesting it could be an effective PET tracer for tumor imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and evaluation of l-5-(2-[(18)F]fluoroethoxy)tryptophan as a new PET tracer. Li, R., Wu, SC., Wang, SC., et al.[2016]

L-1-[18F]FETrp, a fluorine-18 labeled tryptophan analog, effectively accumulates in various cancers such as prostate, lung, and glioma, demonstrating its potential as a promising radiotracer for PET imaging.

The study showed that L-1-[18F]FETrp can differentiate between lung cancer subtypes and successfully crosses the blood-brain barrier to visualize gliomas, indicating its versatility and efficacy in cancer imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of L-1-[18F]Fluoroethyl-Tryptophan for PET Imaging of Cancer. Xin, Y., Gao, X., Liu, L., et al.[2020]

The study introduces a new and simpler method for synthesizing tryptophan-based PET agents using photoredox radiofluorination, which could enhance the monitoring of tryptophan metabolism in diseases like cancer.

The novel 18F-labeled tryptophan analog l-[18F]T13 demonstrated significant tumor uptake in small animal imaging, suggesting its potential for use in monitoring immunotherapy effectiveness in melanoma treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of [18F]F-5-OMe-Tryptophans through Photoredox Radiofluorination: A New Method to Access Tryptophan-Based PET Agents. Wu, X., Ma, X., Zhong, Y., et al.[2023]

References

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

Radiosynthesis and biological evaluation of 5-(3-[18F]fluoropropyloxy)-L-tryptophan for tumor PET imaging. [2016]

2. France pubmed.ncbi.nlm.nih.gov

Synthesis and biological evaluation of ¹⁸F-labeled fluoropropyl tryptophan analogs as potential PET probes for tumor imaging. [2015]

3. England pubmed.ncbi.nlm.nih.gov

Preclinical evaluation of 5-([11C]-methyloxy)-L-tryptophan as a potential PET molecular imaging probe. [2019]

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

Fluorine-18-Labeled PET Radiotracers for Imaging Tryptophan Uptake and Metabolism: a Systematic Review. [2021]

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

Synthesis and biological evaluation of (18)F-labeled Fluoroethoxy tryptophan analogues as potential PET tumor imaging agents. [2020]

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

Discovery of 7-[18F]Fluorotryptophan as a Novel Positron Emission Tomography (PET) Probe for the Visualization of Tryptophan Metabolism in Vivo. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Synthesis and evaluation of l-5-(2-[(18)F]fluoroethoxy)tryptophan as a new PET tracer. [2016]

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

Evaluation of L-1-[18F]Fluoroethyl-Tryptophan for PET Imaging of Cancer. [2020]

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

Development of [18F]F-5-OMe-Tryptophans through Photoredox Radiofluorination: A New Method to Access Tryptophan-Based PET Agents. [2023]