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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to improve imaging techniques for cancer patients by using a special tracer to help doctors better distinguish between tumor and non-tumor areas. By employing 1-(2-[18F]FLUOROETHYL)-L-Tryptophan (a special imaging tracer) in PET/CT scans, researchers hope to plan treatments more accurately based on the tracer absorption by the tumor. The trial seeks participants diagnosed with certain types of cancer, such as brain tumors, neuroendocrine tumors, breast cancer, or rectal cancer, who can undergo imaging procedures. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to experience this innovative imaging approach.

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 prior data suggests that this imaging technique is safe for cancer patients?

Research has shown that 1-(2-[18F]FLUOROETHYL)-L-Tryptophan, a special substance used in PET scans, appears safe based on tests in people. Earlier studies used this substance to create images of human brain tumors and demonstrated initial safety. The substance targets specific enzymes related to tryptophan, helping to distinguish tumor tissue from normal tissue. This assists doctors in assessing treatment effectiveness.

While further research is needed to fully confirm its safety, its prior use in people offers some reassurance. As in any clinical trial, researchers will closely monitor participants for any side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard imaging techniques like CT or MRI that provide structural details of tumors, the [18F]FETrp PET radiotracer is unique because it offers a more detailed look at the metabolic activity of cancer cells. Researchers are excited about this treatment because it uses a special tracer, 1-(2-[18F]FLUOROETHYL)-L-Tryptophan, which targets the amino acid tryptophan involved in cancer metabolism. This could lead to more precise detection and characterization of both intra- and extracranial cancers, potentially catching them earlier and with greater accuracy than current methods.

What evidence suggests that this imaging technique is effective for cancer?

Research has shown that 1-(2-[18F]FLUOROETHYL)-L-Tryptophan, or [18F]FETrp, serves as a promising tool for cancer imaging. In this trial, all participants will receive the [18F]FETrp PET radiotracer to evaluate its uptake in intra- and extracranial cancers. This tracer highlights areas where cancer cells absorb more tryptophan, an amino acid, than normal cells. Studies have demonstrated that this can help doctors see tumors more clearly and plan better treatments. The tracer is produced reliably and meets the necessary standards for clinical use. This method may help distinguish between tumor and non-tumor tissue, potentially improving cancer treatment planning. ^{1 2 6 7 8}

Who Is on the Research Team?

Csaba Juhasz, M.D.,Ph.D

Principal Investigator

Barbara Ann Karmanos Cancer Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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 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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10330273/

L-Tryptophan ([18F]FETrp) for PET Imaging of Cancer in ... With a desired fluorine-18 half-life of 109.8 min, 1-(2-[18F]fluoroethyl)-L-tryptophan (L-[18F]FETrp or [18F]FETrp) is one of the most promising ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05556473

NCT05556473 | F-Tryptophan PET/CT in Human Cancers 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 ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0969804319310759

Automated production of 1-(2-[18F]fluoroethyl)-l-tryptophan ... 1-(2-[18F]fluoroethyl)-l-tryptophan was produced with high reliability and meeting criteria for clinical use. · The radiotracer production features a small ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7064410/

Fluorine-18-labeled PET Radiotracers for Imaging Tryptophan ... Five tracers showed promise for imaging IDO activity, including 1-(2-[18F]fluoroethyl)-L-tryptophan and a F-18 labeled analog of alpha-[11C]methyl-L-tryptophan ...

5. ejnmmipharmchem.springeropen.com ejnmmipharmchem.springeropen.com/articles/10.1186/s41181-024-00256-0

18F]FETrp, a radiotracer for PET imaging of indoleamine 2 ... This work aims to develop a short, epimerization-free and efficient automated procedure of (S)-[ 18 F]FETrp from a corresponding enantiopure tosylate precursor.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11934337/

The First Human Application of an F-18-labeled ... The study provides proof-of-principle data for the safety and potential clinical value of 18 F-FETrp-PET for molecular imaging of human gliomas.

7. researchgate.net researchgate.net/publication/370402388_Automated_Radiosynthesis_of_1-2-18_FFluoroethyl-L-Tryptophan_18_FFETrp_for_PET_Imaging_of_Cancer_in_Humans

L-Tryptophan ([18 F]FETrp) for PET Imaging of Cancer in ... In this work, radiotracer 1-(2-[18F]fluoroethyl)-L-tryptophan (1-L-[18F]FETrp) and its enantioisomer 1-D-[18F]FETrp were synthesized and ...

8. semanticscholar.org semanticscholar.org/paper/Fluorine-18-Labeled-PET-Radiotracers-for-Imaging-a-John-Muzik/d0597c369363f336bcca7eca5d964d12886e2d59

Fluorine-18-Labeled PET Radiotracers for Imaging ... Most F-18-labeled tryptophan derivative PET tracers share common transport mechanisms and biodistribution characteristics, and several reported tracers ...