Fluorine F 18 Fluorthanatrace PET/CT Imaging for Breast Cancer
Recruiting in Palo Alto (17 mi)
+2 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: M.D. Anderson Cancer Center
Disqualifiers: Pregnancy, Breastfeeding, Prior cancer therapy, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?This phase II trial tests whether \[18F\]FluorThanatrace by positron emission tomography (PET)/computed tomography (CT) can improve imaging techniques in patients with breast cancer undergoing a standard of care biopsy or surgery. \[18F\]FluorThanatrace is a new radioactive tracer, which is a type of imaging agent that is labeled with a radioactive tag and injected into the body to help with imaging scans. PET is an established imaging technique that utilizes small amounts of radioactivity attached to very minimal amounts of tracer, in the case of this research, \[18F\]FluorThanatrace. Because some cancers take up \[18F\]FluorThanatrace it can be seen with PET. CT utilizes x-rays that traverse body from the outside. CT images provide an exact outline of organs and potential inflammatory tissue where it occurs in patient's body. \[18F\]FluorThanatrace by PET/CT may help detect the activity of a certain enzyme in the body that may be related to cancer growth in patients with breast cancer.
Will I have to stop taking my current medications?
The trial protocol does not specify whether you need to stop taking your current medications. However, if you are undergoing any current or prior therapy for breast cancer, you may not be eligible to participate.
What data supports the effectiveness of the treatment Fluorine F 18 Fluorthanatrace for breast cancer?
Fluorine 18 fluorthanatrace (18F-FTT) is a PET radiotracer that helps image a protein called PARP-1, which is important in breast cancer. Initial studies have shown it can measure PARP-1 levels in breast cancer patients, suggesting it might help in understanding the disease better.
12345Is Fluorine F 18 Fluorthanatrace safe for use in humans?
Fluorine 18 (18F) fluorthanatrace has been evaluated in early human imaging studies, and while the research primarily focuses on its development and potential as an imaging tool, it does not report any specific safety concerns in humans.
16789How is Fluorine F 18 Fluorthanatrace PET/CT Imaging unique for breast cancer treatment?
Fluorine F 18 Fluorthanatrace is unique because it is a PET radiotracer specifically designed to image PARP-1, a protein involved in DNA repair, which is a target for certain breast cancer drugs. This imaging technique helps visualize the expression levels of PARP-1 in breast cancer, providing a novel way to assess the presence and activity of this protein in tumors.
16101112Eligibility Criteria
This trial is for adults over 18 with breast cancer who are candidates for primary breast surgery and have a tumor of at least 1.0 cm visible on imaging. It's not for those pregnant, breastfeeding, previously treated for their breast cancer, unable to tolerate imaging procedures, or with conditions that may compromise safety or participation.Inclusion Criteria
Participants must be informed of the investigational nature of this study and provide written informed consent, in accordance with institutional and federal guidelines prior to study-specific procedures
I am 18 years old or older.
I am a candidate for surgery to remove breast cancer.
+1 more
Exclusion Criteria
I have received treatment for my primary breast cancer.
I don't have any health issues that a doctor thinks would make the study unsafe for me.
I am not pregnant or breastfeeding.
+1 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Baseline Imaging
Participants receive [18F]FTT intravenously and undergo PET/CT scan over 20-30 minutes
1 day
1 visit (in-person)
Optional Follow-up Imaging
Participants may undergo an optional PET/CT scan 1 week after the baseline scan
1 week
1 visit (in-person, optional)
Follow-up
Participants are monitored for safety and effectiveness after imaging
4 weeks
Participant Groups
[18F]FluorThanatrace by PET/CT is being tested to see if it can improve imaging in patients undergoing biopsy or surgery for breast cancer. This new radioactive tracer might help detect enzyme activity related to cancer growth when used with PET/CT scans.
1Treatment groups
Experimental Treatment
Group I: Treatment ([18F]FTT PET/CT)Experimental Treatment3 Interventions
Patients receive \[18F\]FTT IV over a few seconds to a minute and then undergo PET/CT scan over 20-30 minutes at baseline and another optional scan 1 week later. During the \[18F\]FTT PET/CT scan patients.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of PennsylvaniaPhiladelphia, PA
University of Pennsylvania/Abramson Cancer CenterPhiladelphia, PA
Siteman Cancer Center at Washington UniversitySaint Louis, MO
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Who Is Running the Clinical Trial?
M.D. Anderson Cancer CenterLead Sponsor
National Cancer Institute (NCI)Collaborator
Trevarx Biomedical, IncCollaborator
References
The Development of 18F Fluorthanatrace: A PET Radiotracer for Imaging Poly (ADP-Ribose) Polymerase-1. [2023]Fluorine 18 (18F) fluorthanatrace (18F-FTT) is a PET radiotracer for imaging poly (adenosine diphosphate-ribose) polymerase-1 (PARP-1), an important target for a class of drugs known as PARP inhibitors, or PARPi. This article describes the stepwise development of this radiotracer from its design and preclinical evaluation to the first-in-human imaging studies and the initial validation of 18F-FTT as an imaging-based biomarker for measuring PARP-1 expression levels in patients with breast and ovarian cancer. A detailed discussion on the preparation and submission of an exploratory investigational new drug application to the Food and Drug Administration is also provided. Additionally, this review highlights the need and future plans for identifying a commercialization strategy to overcome the major financial barriers that exist when conducting the multicenter clinical trials needed for approval in the new drug application process. The goal of this article is to provide a road map that scientists and clinicians can follow for the successful clinical translation of a PET radiotracer developed in an academic setting. Keywords: Molecular Imaging-Cancer, PET, Breast, Genital/Reproductive, Chemistry, Radiotracer Development, PARPi, 18F-FTT, Investigational New Drug © RSNA, 2022.
[Imaging of cancer activity and range of tumor involvement--applying to breast cancer]. [2016]In recent years, PET using mainly fluorine-18 fluorodeoxyglucose (FDG) has played a very large role in the management of breast cancer. Systemic, functional images can be obtained by whole body PET and can provide information that is not obtained by anatomical imaging modalities such as conventional X-ray computed tomography, X-ray mammography, or ultrasonography. The utility of FDG-PET for breast cancer patients has been established in every phase of the management of breast cancer, such as the differential diagnosis of breast cancer primary lesion, cancer staging, and posttreatment monitoring. For whole body FDG-PET that can assess the spread of systemic disease in a single examination, postoperative monitoring is one of the most useful applications in particular. In addition, the usefulness of PET for prediction of prognosis and assessment of treatment response has been reported along with the medical economical effect of FDG-PET for breast cancer patients. Moreover, it is expected that a new tracer other than FDG, such as fluorine-18 ion and [18F]-fluoro-17beta; estradiol (FES), and the new instruments such as PET-CT and positron emission mammography (PEM) can further contribute to the management of breast cancer. In this report, we will outline the benefits, limitations, and future prospects of PET for breast cancer.
Translation of New Molecular Imaging Approaches to the Clinical Setting: Bridging the Gap to Implementation. [2016]Molecular imaging with PET is a rapidly emerging technique. In breast cancer patients, more than 45 different PET tracers have been or are presently being tested. With a good rationale, after development of the tracer and proven feasibility, it is of interest to evaluate whether there is a potential meaningful role for the tracer in the clinical setting-such as in staging, in the (early) prediction of a treatment response, or in supporting drug choices. So far, only (18)F-FDG PET has been incorporated into breast cancer guidelines. For proof of the clinical relevance of tracers, especially for analysis in a multicenter setting, standardization of the technology and access to the novel PET tracer are required. However, resources for PET implementation research are limited. Therefore, next to randomized studies, novel approaches are required for proving the clinical value of PET tracers with the smallest possible number of patients. The aim of this review is to describe the process of the development of PET tracers and the level of evidence needed for the use of these tracers in breast cancer. Several breast cancer trials have been performed with the PET tracers (18)F-FDG, 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT), and (18)F-fluoroestradiol ((18)F-FES). We studied them to learn lessons for the implementation of novel tracers. After defining the gap between a good rationale for a tracer and implementation in the clinical setting, we propose solutions to fill the gap to try to bring more PET tracers to daily clinical practice.
Breast cancer therapy: the role of PET-CT in decision making. [2009]This paper describes the role of positron emission tomography (PET) and PET-computed tomography (CT) in breast cancer patients. Fluorine-18-Fluoro-D-glucose (FDG) has limited diagnostic value in detecting small noninvasive primary tumors, in staging the axillary region in early stages and in the detection of osteoblastic metastases. Better results have been shown in the detection and staging of primary invasive tumors. Significant clinical data are available in the monitoring of primary chemotherapy in locally advanced breast cancer where [(18)F]FDG PET-CT allows prediction of the response even shortly after the onset of therapy. Quantitative evaluation of tumor uptake is necessary. Therapy-induced changes in tumor metabolism may be helpful in making decisions about continuation, modification or cessation of therapy. Therefore, [(18)F]FDG PET-CT appears to be a promising tool for the personalization of breast cancer treatment by its early identification of nonresponders. It offers improved patient care, avoiding ineffective chemotherapy and the side effects while reducing the cost. An area generating high expectations for PET-TC in breast cancer is in monitoring in order to tailor therapy to the tumor characteristics of individual patients who may require tracers other than [(18)F]FDG. The introduction of new PET tracers and the development of new instruments will offer opportunities to improve the role of PET-CT in decision making of therapy in these patients.
Accuracy of 18F-NaF PET/CT in bone metastasis detection and its effect on patient management in patients with breast carcinoma. [2019]Determination of the accuracy of sodium fluorine-18-fluoride (F-NaF) PET/computed tomography (CT) for the evaluation of bone metastases, and the impact on patient management in breast cancer patients.
Synthesis of [18F]fluoroalanine and [18F]fluorotamoxifen for imaging breast tumors. [2016]To develop ligands for imaging breast tumors, [18F]fluoro analogue of tamoxifen and [18F]fluoroalanine were radiosynthesized. In vivo biodistribution studies were performed in mammary tumor-bearing rats. In studies on the biodistribution of an [18F]fluoro analogue of tamoxifen, tumor uptake decreased when rats were pretreated with diethylstilbestrol (DES), suggesting that tracer uptake in tumors was receptor-mediated. An estrogen receptor assay indicated that tumors have a receptor density of 7.5 fmol/mg protein. Studies of the distribution of [18F]fluoroalanine in tissue showed that the tumor-to-tissue ratio increases as a function of time. Positron emission tomography (PET) images of tumor-bearing rats demonstrated that tumors can be visualized 1 h after rats are injected with an [18F]fluoro analogue of tamoxifen. PET imaging of pigs after injection of 10 mCi of [18F]fluoro analogue of tamoxifen showed uterine uptake that could be blocked by DES (50 mg). The findings suggest that both radiotracers are useful for imaging breast tumors.
(18)F-labeled positron emission tomographic radiopharmaceuticals in oncology: an overview of radiochemistry and mechanisms of tumor localization. [2022]Molecular imaging is the visualization, characterization, and measurement of biological processes at the molecular and cellular levels in a living system. At present, positron emission tomography/computed tomography (PET/CT) is one the most rapidly growing areas of medical imaging, with many applications in the clinical management of patients with cancer. Although [(18)F]fluorodeoxyglucose (FDG)-PET/CT imaging provides high specificity and sensitivity in several kinds of cancer and has many applications, it is important to recognize that FDG is not a "specific" radiotracer for imaging malignant disease. Highly "tumor-specific" and "tumor cell signal-specific" PET radiopharmaceuticals are essential to meet the growing demand of radioisotope-based molecular imaging technology. In the last 15 years, many alternative PET tracers have been proposed and evaluated in preclinical and clinical studies to characterize the tumor biology more appropriately. The potential clinical utility of several (18)F-labeled radiotracers (eg, fluoride, FDOPA, FLT, FMISO, FES, and FCH) is being reviewed by several investigators in this issue. An overview of design and development of (18)F-labeled PET radiopharmaceuticals, radiochemistry, and mechanism(s) of tumor cell uptake and localization of radiotracers are presented here. The approval of clinical indications for FDG-PET in the year 2000 by the Food and Drug Administration, based on a review of literature, was a major breakthrough to the rapid incorporation of PET into nuclear medicine practice, particularly in oncology. Approval of a radiopharmaceutical typically involves submission of a "New Drug Application" by a manufacturer or a company clearly documenting 2 major aspects of the drug: (1) manufacturing of PET drug using current good manufacturing practices and (2) the safety and effectiveness of a drug with specific indications. The potential routine clinical utility of (18)F-labeled PET radiopharmaceuticals depends also on regulatory compliance in addition to documentation of potential safety and efficacy by various investigators.
Fluorinated tracers for imaging cancer with positron emission tomography. [2018]2-[18F]fluoro-2-deoxy-D-glucose (FDG) is currently the only fluorinated tracer used in routine clinical positron emission tomography (PET). Fluorine-18 is considered the ideal radioisotope for PET imaging owing to the low positron energy (0.64 MeV), which not only limits the dose rate to the patient but also results in a relatively short range of emission in tissue, thereby providing high-resolution images. Further, the 110-min physical half-life allows for high-yield radiosynthesis, transport from the production site to the imaging site and imaging protocols that may span hours, which permits dynamic studies and assessment of potentially fairly slow metabolic processes. The synthesis of fluorinated tracers as an alternative to FDG was initially tested using nucleophilic fluorination of the molecule, as performed when radiolabelling with iodine-124 or bromide-76. However, in addition to being long, with multiple steps, this procedure is not recommended for bioactive molecules containing reactive groups such as amine or thiol groups. Radiochemical yields are also often low. More recently, radiosynthesis from prosthetic group precursors, which allows easier radiolabelling of biomolecules, has led to the development of numerous fluorinated tracers. Given the wide availability of 18F, such tracers may well develop into important routine tracers. This article is a review of the literature concerning fluorinated radiotracers recently developed and under investigation for possible PET imaging in cancer patients. Two groups can be distinguished. The first includes "generalist" tracers, i.e. tracers amenable to use in a wide variety of tumours and indications, very similar in this respect to FDG. These are tracers for non-specific cell metabolism, such as protein synthesis, amino acid transport, nucleic acid synthesis or membrane component synthesis. The second group consists of "specific" tracers for receptor expression (i.e. oestrogens or somatostatin), cell hypoxia or bone metabolism.
Synthesis and biological evaluation of 2-(3,4-dimethoxyphenyl)-6-(2-[18F]fluoroethoxy)benzothiazole ([18F]FEDBT) for PET imaging of breast cancer. [2017]Given the ever-present demand for improved PET radiotracer in oncology imaging, we have synthesized 2-(3,4-dimethoxyphenyl)-6-(2-[18F]fluoroethoxy)benzothiazole ([18F]FEDBT), a fluorine-18-containing fluoroethylated benzothiazole to explore its utility as a PET imaging tracer. [18F]FEDBT was prepared via kryptofix-mediated nucleophilic substitution of the tosyl group precursor. Fractionated ethanol-based solid-phase (SPE cartridge-based) purification afforded [18F]FEDBT in 60% radiochemical yield (EOB), with radiochemical purity in excess of 98% and the specific activity was 35GBq/μmol. The radiotracer displayed clearly higher cellular uptake ratio in various breast cancer cell lines MCF7, MDA-MB-468 and MDA-MB-231. However, both biodistribution and microPET studies have showed an higher abdominal accumulation of [18F]FEDMBT and the tumor/muscle ratio of 1.8 was observed in the MDA-MB-231 xenograft tumors mice model. Further the lipophilic improvement is needed for the reducement of hepatobilliary accumulation and to promote the tumor uptake for PET imaging of breast cancer.
[Development of molecular imaging probes in oncology]. [2016]Molecular imaging probes used for positron emission tomography(PET)in oncology are reviewed. Although [18F] FDG is presently the most useful probe for imaging tumors, there is a need for complementary probes of FDG with some limitations on detection in the brain or inflammatory region. The review is mostly focused on 18F-labeled probes designed for amino acid transport and protein synthesis, DNA synthesis, membrane lipid, and hypoxia such as FET, FLT, FMAU, fluorocholine, and FMISO, together with our original probes of FMT and FRP-170.
[The use of 18F-fluorothymidine and 18F-fluorocholine in imaging with positron emission tomography]. [2018]Positron emission tomography (PET) with (18)F-fluorodeoxyglucose ((18)F-FDG) has proven useful for diagnosis, staging, restaging and therapy monitoring in a variety of tumors. Nevertheless there are some limitations. (18)F-FDG is not tumor selective and shows accumulation in inflammatory cells such as macrophages and fibroblasts that require glucose as their substrate for energy production. Furthermore, tissues with high background, such as brain may cause difficulties in image interpretation. Moreover, there are some tumors that are not avid for (18)F-FDG such as prostate cancer, hepatocellular carcinoma and some slow-growing tumors. This limitations motivated efforts to develop new oncologic tracers for PET imaging. Recently, (18)F-fluorothymidine ((18)F-FLT), a radiolabeled analog of thymidine, has been synthesized for imaging tumor cell proliferation. Another tracer that has been synthesized is (18)F-fluorocholine ((18)F-FCH) that can incorporate into tumor cell membranes by metabolic trapping. The purpose of this article is to report the role of these two new radiopharmaceuticals for PET imaging, (18)F-FLT and (18)F-FCH in the management of various malignancies.
Positron emission tomography in patients with breast cancer using (18)F-3'-deoxy-3'-fluoro-l-thymidine ((18)F-FLT)-a pilot study. [2016]This pilot study investigated the feasibility of (18)F-3'-deoxy-3'-fluoro-l-thymidine ((18)F-FLT) as a positron emission tomography (PET) tracer for the visualisation of breast cancer.