F-Tryptophan PET/CT Imaging for Cancer
Recruiting in Palo Alto (17 mi)
Overseen byCsaba Juhasz, M.D.,Ph.D
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
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
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.
12345Is 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.
25678How 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.
12459Eligibility 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
+10 more
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.
+5 more
Trial 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
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: [18F]FETrp PET radiotracerExperimental Treatment1 Intervention
All participants will receive the tracer to evaluate the uptake of \[18F\]FETrp PET/CT on intra- and extracranial cancers.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Karmanos Cancer InstituteDetroit, MI
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Who Is Running the Clinical Trial?
Barbara Ann Karmanos Cancer InstituteLead Sponsor
Washington University School of MedicineCollaborator
References
Radiosynthesis and biological evaluation of 5-(3-[18F]fluoropropyloxy)-L-tryptophan for tumor PET imaging. [2016][(18)F]FDG PET has difficulty distinguishing tumor from inflammation in the clinic because of the same high uptake in nonmalignant and inflammatory tissue. In contrast, amino acid tracers do not accumulate in inflamed tissues and thus provide an excellent opportunity for their use in clinical cancer imaging. In this study, we developed a new amino acid tracer 5-(3-[(18)F]Fluoropropyloxy)-L-tryptophan ([(18)F]-L-FPTP) by two-step reactions and performed its biologic evaluation.
Synthesis and biological evaluation of ¹⁸F-labeled fluoropropyl tryptophan analogs as potential PET probes for tumor imaging. [2015]In the search for an efficient, fluorine-18 labeled amino acid based radiotracer for tumor imaging with positron emission tomography (PET), two new tryptophan analogs were synthesized and characterized in vitro and in vivo. Both are tryptophan alkyl-derivatives, namely 2-(3-[(18)F]fluoropropyl)-DL-tryptophan ([(18)F]2-FPTRP) and 5-(3-[(18)F]fluoro-propyl)-DL-tryptophan ([(18)F]5-FPTRP). Standard reference compounds and precursors were prepared by multi step approaches. Radiosynthesis was achieved by no-carrier-added nucleophilic [(18)F]fluorination in 29-34% decay corrected yields with radiochemical purity over 99%. In vitro cell uptake assays showed that both compounds are substrates for amino acid transport and enter small cell lung cancer cells (NCI-H69) most probably almost exclusively via large neutral amino acids transporter(s) (LAT). Small animal PET imaging with xenograft bearing mice revealed high tumor/background ratios for [(18)F]2-FPTRP comparable to the well established tyrosine analog O-(2-[(18)F]fluroethyl)-L-tyrosine ([(18)F]FET). Radiometabolite studies showed no evidence of involvement of a biotransformation step in tumor accumulation.
Preclinical evaluation of 5-([11C]-methyloxy)-L-tryptophan as a potential PET molecular imaging probe. [2019]The new tumor probe 5-([C]-methyloxy)-L-tryptophan ([C]-L-CMTP) had been found to show high uptake in tumor tissue in our previous report; however, the pharmacokinetic properties of [C]-L-CMTP have not been characterized. In this present study, we evaluated the potential of [C]-L-CMTP as a PET probe for tumor imaging.
Fluorine-18-Labeled PET Radiotracers for Imaging Tryptophan Uptake and Metabolism: a Systematic Review. [2021]Due to its metabolism via the serotonin and kynurenine pathways, tryptophan plays a key role in multiple disease processes including cancer. Imaging tryptophan uptake and metabolism in vivo can be achieved with tryptophan derivative positron emission tomography (PET) radiotracers. While human studies with such tracers have been confined to C-11-labeled compounds, preclinical development of F-18-labeled tryptophan-based radiotracers has surged in recent years. We performed a systematic review of studies reporting on such F-18-labeled tryptophan tracers to summarize and compare their biological characteristics and their potential for tumor imaging, with a particular focus on key enzymes of the kynurenine pathway (indoleamine 2,3-dioxygenase [IDO] and tryptophan 2,3-dioxygenase [TDO]), which play an important role in tumoral immune resistance. From a PubMed search, English language articles including data on the preparation and radiochemical and/or biological characteristics of F-18-labeled tryptophan derivative radiotracers were reviewed. A total of 19 original papers included data on 15 unique radiotracers, the majority of which were synthesized with an adequate radiochemical yield. Automated synthesis was reported for 1-(2-[18F]fluoroethyl)-L-tryptophan, the most extensively evaluated tracer thus far. Biodistribution studies showed high uptake in the pancreas, while the L-type amino acid transporter was the dominant transport mechanism for most of the reviewed tracers. Tracers tested for tumor uptake showed accumulation in tumor cell lines in vitro and in xenografts in vivo, often with favorable tumor-to-background uptake ratios in comparison with clinically used F-18-labeled radiotracers. 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 tested clinically in previous studies. Two radiotracers were metabolized by TDO but showed defluorination in vivo. In summary, most F-18-labeled tryptophan derivative PET tracers share common transport mechanisms and biodistribution characteristics. Several reported tracers could be candidates for further testing and validation toward PET imaging applications in a variety of human diseases.
Synthesis and biological evaluation of (18)F-labeled Fluoroethoxy tryptophan analogues as potential PET tumor imaging agents. [2020]As a continuation of our research efforts toward the development of tryptophan-based radiotracers for tumor imaging with positron emission tomography (PET), three new fluoroethoxy tryptophan analogues were synthesized and evaluated in vivo. These new tracers (namely, 4-(2-[(18)F]fluoroethoxy)-dl-tryptophan ([(18)F]4-FEHTP), 6-(2-[(18)F]fluoroethoxy)-dl-tryptophan ([(18)F]6-FEHTP), and 7-(2-[(18)F]fluoroethoxy)-dl-tryptophan ([(18)F]7-FEHTP) carry the fluoroethoxy side chain either at positions 4-, 6-, or 7- of the indole core. Reference compounds and precursors were synthesized by multistep approaches. Radiosynthesis was accomplished by no-carrier-added nucleophilic (18)F-fluorination following either an indirect approach (O-alkylation of the corresponding hydroxytryptophan with [(18)F]fluoroethyltosylate) or a direct approach (nucleophilic [(18)F] fluorination using a protected mesyl precursor). Radiochemical yields (decay corrected) for both methods were in the range of 10-18%. Small animal PET imaging with xenograft-bearing mice revealed the highest tumor/background ratio for [(18)F]6-FEHTP which, in a direct comparison, outperformed the other two tryptophan tracers and also the well-established tyrosine analogue O-(2-[(18)F]fluoroethyl)-l-tyrosine ([(18)F]l-FET). Investigation of the transport mechanism of [(18)F]6-FEHTP in small cell lung cancer cells (NCI-H69) revealed that it is most probably taken up exclusively via the large neutral amino acid transporter(s) (LAT).
Discovery of 7-[18F]Fluorotryptophan as a Novel Positron Emission Tomography (PET) Probe for the Visualization of Tryptophan Metabolism in Vivo. [2019]Tryptophan and its metabolites are involved in different physiological and pathophysiological processes. Consequently, positron emission tomography (PET) tracers addressing tryptophan metabolic pathways should allow the detection of different pathologies like neurological disorders and cancer. Herein we report an efficient method for the preparation of fluorotryptophans labeled in different positions with 18F and their biological evaluation. 4-7-[18F]Fluorotryptophans ([18F]FTrps) were prepared according to a modified protocol of alcohol-enhanced Cu-mediated radiofluorination in 30-53% radiochemical yields. In vitro experiments demonstrated high cellular uptake of 4-7-[18F]FTrps in different tumor cell lines. 4, 5-, and 6-[18F]FTrps, although stable in vitro, suffered from rapid in vivo defluorination. In contrast, 7-[18F]FTrp demonstrated a high in vivo stability and enabled a clear delineation of serotonergic areas and melatonin-producing pineal gland in rat brains. Moreover 7-[18F]FTrp accumulated in different tumor xenografts in a chick embryo CAM model. Thus, 7-[18F]FTrp represents a highly promising PET probe for imaging of Trp metabolism.
Synthesis and evaluation of l-5-(2-[(18)F]fluoroethoxy)tryptophan as a new PET tracer. [2016]A convenient remote controlled synthesis of a new tryptophan analog, l-5-(2-[(18)F] fluoroethoxy)-tryptophan (5-(18)FEHTP) was described. The radiochemical yield within 65min was about 12-16% without decay correction, the radiochemical purity was over 98%, and 5-(18)FEHTP dissolved in saline was stable over 6h at room temperature. The biodistribution of 5-(18)FEHTP in mice and the high uptake of 5-(18)FEHTP in tumor demonstrated that it is very likely a new PET tracer for tumor imaging.
Evaluation of L-1-[18F]Fluoroethyl-Tryptophan for PET Imaging of Cancer. [2020]Label="PURPOSE">Fluorine-18 labeled tryptophan analog L-1-[18F]fluoroethyl-tryptophan (L-1-[18F]FETrp) was designed for positron emission tomography (PET) imaging of cancer by dual targeting of the overexpressed amino acid transporters and altered indoleamine 2,3-dioxygenase (IDO)-mediated kynurenine pathway of tryptophan metabolism. In our previous study, we described the radiosynthesis and preliminary evaluation of L-1-[18F]FETrp for PET imaging of breast cancer. The aim of this study was to investigate the in vivo imaging mechanism and further evaluate this radiotracer in more wide range types of cancers including prostate cancer, lung cancer, and glioma.
Development of [18F]F-5-OMe-Tryptophans through Photoredox Radiofluorination: A New Method to Access Tryptophan-Based PET Agents. [2023]Although various radiolabeled tryptophan analogs have been developed to monitor tryptophan metabolism using positron emission tomography (PET) for various human diseases including melanoma and other cancers, their application can be limited due to the complicated synthesis process. In this study, we demonstrated that photoredox radiofluorination represents a simple method to access novel tryptophan-based PET agents. In brief, 4-F-5-OMe-tryptophans (l/d-T13) and 6-F-5-OMe-tryptophans (l/d-T18) were easily synthesized. The 18F-labeled analogs were produced by photoredox radiofluorination with radiochemical yields ranging from 2.6 ± 0.5% to 32.4 ± 4.1% (3 ≤ n ≤ 5, enantiomeric excess ≥ 99.0%) and over 98.0% radiochemical purity. Small animal imaging showed that l-[18F]T13 achieved 9.58 ± 0.26%ID/g tumor uptake and good contrast in B16F10 tumor-bearing mice (n = 3). Clearly, l-[18F]T13 exhibited prominent tumor uptake, warranting future evaluations of its potential usage in precise immunotherapy monitoring.