FMISO Imaging for Brain Cancer
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: OHSU Knight Cancer Institute
Disqualifiers: Pregnancy, Claustrophobia, Metallic implants, others
No Placebo Group
Prior Safety Data
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?This phase II trial studies how well ¹⁸F- fluoromisonidazole (FMISO) works with positron emission tomography (PET)/magnetic resonance imaging (MRI) in assessing participants with malignant (cancerous) brain tumors. FMISO provides information about the oxygen levels in a tumor, which may affect how the tumor behaves. PET/MRI imaging produces images of the brain and how the body functions. FMISO PET/MRI may help investigators see how much oxygen is getting in the brain tumors.
Will I have to stop taking my current medications?
The trial information 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 18F-Fluoromisonidazole (FMISO) for brain cancer?
Research shows that FMISO is effective in identifying hypoxic (low oxygen) areas in tumors, which are often resistant to treatment. This ability to detect hypoxia can help in planning more effective treatment strategies for brain cancer.
12345Is FMISO imaging safe for humans?
The available research primarily involves animal studies, which do not provide direct evidence of safety in humans. However, FMISO has been used in clinical applications for decades to study oxygen levels in cancer cells, suggesting a history of use in humans.
12678How is the drug ¹⁸F-Fluoromisonidazole (¹⁸F-FMISO) unique for brain cancer treatment?
¹⁸F-Fluoromisonidazole (¹⁸F-FMISO) is unique because it is a radiotracer used in PET scans to detect low-oxygen areas (hypoxia) in tumors, which can help doctors understand how the cancer might respond to treatments like radiotherapy and chemotherapy. This approach is different from standard treatments as it provides detailed imaging of tumor oxygen levels, which is crucial for planning effective treatment strategies.
2691011Eligibility Criteria
This trial is for adults over 18 with known or suspected brain tumors who can consent to the study. They should have a performance score indicating they're fairly active and able to care for themselves, and either planning or have had treatment for their tumor. Pregnant individuals, those with severe kidney issues, claustrophobia, certain allergies, or conditions where oxygen therapy could be harmful are excluded.Inclusion Criteria
My legal representative has agreed to my participation in this study.
I have a brain lesion larger than 10 mL suspected to be cancer.
Able to provide informed written consent and/or acceptable surrogate capable of providing consent on the patient's behalf
+3 more
Exclusion Criteria
You are not sure if you are pregnant according to the guidelines of the Department of Radiology and AIRC.
Presence of any other co-existing condition that, in the judgment of the principal investigator, might increase the risk to the subject (i.e., plans for hospice or end of life care)
I cannot undergo PET, MRI, or certain contrast agent procedures.
+11 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Diagnostic Imaging
Participants receive FMISO intravenously and undergo dynamic and static PET/CT or PET/MRI scans to assess tumor oxygen levels and imaging metrics.
1 day
1 visit (in-person)
Retest Examination
Participants undergo a retest examination within 7 days to assess reproducibility of imaging metrics.
1 week
1 visit (in-person)
Follow-up
Participants are monitored for safety and effectiveness of imaging metrics, with potential additional scans every 4 weeks.
Up to 5 years
Participant Groups
The trial tests how well FMISO works with PET/MRI scans in assessing malignant brain tumors by showing oxygen levels within the tumor. This may help understand the tumor's behavior better and improve imaging techniques.
1Treatment groups
Experimental Treatment
Group I: Diagnostic (FMISO, PET/MRI or PET/CT)Experimental Treatment5 Interventions
Participants receive FMISO intravenously (IV). Participants also undergo dynamic PET/computed tomography (CT) or PET/MRI over 120 minutes beginning 1 minute prior to FMISO injection, and static PET/CT or PET/MRI over 20-40 minutes approximately 90 minutes after FMISO injection. Participants then undergo a retest examination within 7 days. Participants may undergo 2 more PET/MRI or PET/CT scans no sooner than every 4 weeks. Supplemental oxygen may be administered to effect MRI signal.
¹⁸F-Fluoromisonidazole is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as ¹⁸F-FMISO for:
- Diagnostic imaging for malignant brain tumors
🇪🇺 Approved in European Union as ¹⁸F-FMISO for:
- Diagnostic imaging for malignant brain tumors
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
OHSU Knight Cancer InstitutePortland, OR
Who Is Running the Clinical Trial?
OHSU Knight Cancer InstituteLead Sponsor
National Cancer Institute (NCI)Collaborator
Weill Cornell UniversityCollaborator
Oregon Health and Science UniversityCollaborator
References
Comparison of the distribution of fluorine-18 fluoromisonidazole, deoxyglucose and methionine in tumour tissue. [2019]To evaluate the tumour imaging potential of fluorine-18 fluoromisonidazole (FMISO), we studied FMISO uptake in an experimental tumour model and examined the correlation between intratumoral distributions of FMISO, 14C-2-deoxyglucose (2DG) and 14C-methionine (Met). The study was performed using control rats with the AH109A tumour and rats with the same tumour under local hypoxia. Tumour uptake of FMISO was constant between 30 min and 2 h after injection, and the tumour to muscle ratio was 2 from 2 to 4 h. A tumour study with FMISO was scheduled at 2 h. Double-tracer autoradiography of the tumour demonstrated that in the areas of high FMISO uptake, there was low uptake of Met, while areas of low FMISO uptake showed high Met uptake. FMISO showed high grain density in the rim of the tumour surrounding the necrotic area. 2DG showed a more uniform distribution over the entire section of viable cells. The mean uptake of FMISO by hypoxic, radioresistant tumours was significantly higher than that by the control tumours (P
Synthesis of [18F]FMISO, a hypoxia-specific imaging probe for PET, an overview from a radiochemist's perspective. [2023]Label="BACKGROUND" NlmCategory="BACKGROUND">[18F]fluoromisonidazole ([18F]FMISO, 1H-1-(3-[18F]fluoro-2-hydroxypropyl)-2-nitroimidazole) is a commonly used radiotracer for imaging hypoxic conditions in cells. Since hypoxia is prevalent in solid tumors, [18F]FMISO is in clinical application for decades to explore oxygen demand in cancer cells and the resulting impact on radiotherapy and chemotherapy.
Correlation of Tumor Hypoxia Metrics Derived from 18F-Fluoromisonidazole Positron Emission Tomography and Pimonidazole Fluorescence Images of Optically Cleared Brain Tissue. [2021]18F-fluoromisonidazole (FMISO) positron emission tomography (PET) is a widely used noninvasive imaging modality for assessing hypoxia. We describe the first spatial comparison of FMISO PET with an ex vivo reference standard for hypoxia across whole tumor volumes. Eighteen rats were orthotopically implanted with C6 or 9L brain tumors and made to undergo FMISO PET scanning. Whole brains were excised, sliced into 1-mm-thick sections, optically cleared, and fluorescently imaged for pimonidazole using an in vivo imaging system. FMISO maximum tumor uptake, maximum tumor-to-cerebellar uptake (TCmax), and hypoxic fraction (extracted 110 minutes after FMISO injection) were correlated with analogous metrics derived from pimonidazole fluorescence images. FMISO SUVmax was not significantly different between C6 and 9L brain tumors (P = .70), whereas FMISO TCmax and hypoxic fraction were significantly greater for C6 tumors (P < .01). FMISO TCmax was significantly correlated with the maximum tumor pimonidazole intensity (ρ = 0.76, P < .01), whereas FMISO SUVmax was not. FMISO tumor hypoxic fraction was significantly correlated with the pimonidazole-derived hypoxic fraction (ρ = 0.78, P < .01). Given that FMISO TCmax and tumor hypoxic fraction had strong correlations with the pimonidazole reference standard, these metrics may offer more reliable measures of tumor hypoxia than conventional PET uptake metrics (SUVmax). The voxel-wise correlation between FMISO uptake and pimonidazole intensity for a given tumor was strongly dependent on the tumor's TCmax (ρ = 0.81, P < .01) and hypoxic fraction (ρ = 0.85, P < .01), indicating PET measurements within individual voxels showed greater correlation with pimonidazole reference standard in tumors with greater hypoxia.
Quantifying regional hypoxia in human tumors with positron emission tomography of [18F]fluoromisonidazole: a pretherapy study of 37 patients. [2022]To assess pretreatment hypoxia in a variety of tumors using positron emission tomography (PET) after injection of the hypoxia-binding radiopharmaceutical [18F]fluoromisonidazole ([18F]FMISO).
Evaluation of isocitrate dehydrogenase mutation in 2021 world health organization classification grade 3 and 4 glioma adult-type diffuse gliomas with 18F-fluoromisonidazole PET. [2023]Label="PURPOSE" NlmCategory="OBJECTIVE">This study aimed to investigate the uptake characteristics of 18F-fluoromisonidazole (FMISO), in mutant-type isocitrate dehydrogenase (IDH-mutant, grade 3 and 4) and wild-type IDH (IDH-wildtype, grade 4) 2021 WHO classification adult-type diffuse gliomas.
Evaluation of hypoxic tissue dynamics with 18F-FMISO PET in a rat model of permanent cerebral ischemia. [2021][¹⁸F]Fluoromisonidazole (¹⁸F-FMISO) is a nitroimidazole derivative that has been proposed as a positron emission tomography (PET) radiotracer to detect hypoxic tissue in vivo. This compound accumulates in hypoxic but viable tissue and may be a good candidate for evaluating the ischemic penumbra. We evaluated the time course of ¹⁸F-FMISO uptake using PET in a rat model of permanent cerebral ischemia and the correlation with histological changes.
Dose-response relationships of FMISO between trace dose and various macro-doses in rat by ultra-performance liquid chromatography with mass spectrometry and radioactivity analysis. [2019]Screening the pharmacokinetics of candidates using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) may be efficacious and safe for the research and development of new PET imaging agents. However, the PET imaging agent is administered as trace dose and the sensitivity of LC-MS/MS is often insufficient. If the dose was increased to be quantifiable, it should be necessary to prove whether the pharmacokinetics between trace and macro-doses is consistent or not. In this paper, fluoromisonidazole (FMISO), a tumor PET imaging agent, was chosen to evaluate the dose-response pharmacokinetics by administering various single intravenous doses (0.1, 0.4, 1.6 and 6.4 mg/kg) in male Sprague-Dawley rats. The plasma concentration of FMISO was determined by an ultra-performance liquid chromatography-tandem mass spectrometric (UPLC-MS/MS) method, and the blood radioactivity of [(18)F]FMISO was detected by a gamma counter. By calculating and comparing the pharmacokinetic parameters, the total area under the plasma concentration-time curve from time zero to infinity (AUC(0-∞)) and peak plasma concentration (C(max)) values increased with the selected FMISO doses, and showing linear dose-dependent. On the other hand, some parameters related to time, such as the elimination half-lives (t(1/2)) and elimination rate constant (K(e)) were dose-independent, and there is no significant deference between trace dose and various macro-doses. The data should be useful to evaluate the novel 2-nitroimidazole derivatives as potential PET tumor imaging agents.
Fully automated one-pot synthesis of [18F]fluoromisonidazole. [2022]A (18)F-labeled fluoromisonidazole (1H-1-(3-[(18)F]fluoro-2-hydroxypropyl)-2-nitroimidazole, [(18)F]FMISO) was prepared via a one-pot, two-step synthesis procedure using a modified commercial Tracerlab FX(F-N) synthesis module. Nucleophilic fluorination of the precursor molecule 1-(2'-nitro-1'-imidazolyl)-2-O-tetrahydropyranyl-3-O-toluenesulphonylpropanediol using no-carrier-added [(18)F]fluoride, followed by hydrolysis of the protecting group with 1 mol/L HCl and purification with Sep-Paks instead of HPLC, gave [(18)F]FMISO. The overall radiochemical yield with no decay correction was greater than 40%, the whole synthesis time was less than 40 min and the radiochemical purity was greater than 95%. The new automated synthesis procedure can be applied to the fully automated synthesis of [(18)F]FMISO using a commercial FDG synthesis module.
Influence of the scan time point when assessing hypoxia in 18F-fluoromisonidazole PET: 2 vs. 4 h. [2021]Label="PURPOSE"> 18F-fluoromisonidazole (18F-FMISO) is the most widely used positron emission tomography (PET) tracer for imaging tumor hypoxia. Previous reports suggested that the time from injection to the scan may affect the assessment of 18F-FMISO uptake. Herein, we directly compared the images at 2 h and 4 h after a single injection of 18F-FMISO.
(18)F-fluoromisonidazole (FMISO) Positron Emission Tomography (PET) Predicts Early Infarct Growth in Patients with Acute Ischemic Stroke. [2017](18) F-fluoromisonidazole (FMISO) positron emission tomography (PET) is used to image metabolically compromised but viable hypoxic tissue. We hypothesized that FMISO PET might predict early infarct growth in acute ischemic stroke patients with perfusion-diffusion mismatch in magnetic resonance imaging (MRI).
Fluorine-18-fluoromisonidazole radiation dosimetry in imaging studies. [2016]Fluoromisonidazole (FMISO), labeled with the positron emitter 18F, is a useful hypoxia imaging agent for PET studies, with potential applications in patients with tumors, cardiovascular disease and stroke.