FMISO Imaging for Brain Cancer

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: OHSU Knight Cancer Institute

Disqualifiers: Pregnancy, Claustrophobia, Metallic implants, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new imaging method to measure oxygen levels in brain tumors. Researchers use a special dye, ¹⁸F-Fluoromisonidazole (FMISO), combined with advanced imaging techniques (PET/MRI or PET/CT) to better understand brain tumor behavior. The goal is to determine if this method can guide treatment by showing oxygen levels in tumors. The trial seeks adults with a brain tumor or those who suspect they might have one and have been previously treated or plan to be treated. As a Phase 2 trial, this research focuses on assessing the method's effectiveness in an initial, smaller group, offering participants a chance to contribute to advancements in brain tumor imaging.

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 prior data suggests that FMISO PET/MRI imaging is safe for assessing brain tumors?

Research has shown that ¹⁸F-Fluoromisonidazole (FMISO) is commonly used in PET scans to image low oxygen levels in tumors. This aids doctors in understanding oxygen levels in brain tumors, which is crucial for treatment planning. However, limited safety information is available for humans.

Although FMISO has been used in many studies on various tumor types, specific details about side effects remain poorly documented. FMISO is not a cancer treatment but a tool to understand tumor behavior by highlighting low-oxygen areas.

Since this is a phase 2 trial, earlier research has demonstrated some evidence of FMISO's safety, indicating it is generally safe enough for further human testing. Participants in this study will assist researchers in learning more about FMISO's role in brain tumors, and no major safety concerns are anticipated. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about ¹⁸F-Fluoromisonidazole (FMISO) imaging for brain cancer because it offers a unique way to visualize tumor hypoxia, which is often linked to aggressive tumor growth and resistance to treatment. Unlike current imaging methods, FMISO is a radiotracer that specifically targets low-oxygen areas within the brain tumor, potentially allowing for more precise treatment planning. This technique could improve the accuracy of PET/MRI or PET/CT scans, helping doctors tailor therapies to each patient's specific tumor environment. By identifying these hypoxic regions, FMISO imaging could lead to more effective treatment strategies and better outcomes for patients with brain cancer.

What evidence suggests that FMISO PET/MRI is effective for assessing brain cancer?

Studies have shown that a special imaging agent called ¹⁸F-Fluoromisonidazole (FMISO) effectively detects low oxygen levels in tumors, known as tumor hypoxia. Tumors with low oxygen can be more aggressive. In this trial, participants will receive FMISO intravenously and undergo PET scans to help doctors assess oxygen levels in brain tumors. Research indicates that knowing a tumor's oxygen level can help predict its growth or response to treatment. Various studies have successfully used this imaging method to provide valuable insights into tumor behavior. ^{2 4 6 7 8}

Who Is on the Research Team?

Ramon Barajas

Principal Investigator

OHSU Knight Cancer Institute

Are You a Good Fit for This Trial?

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

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• ¹⁸F-Fluoromisonidazole

Trial Overview 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.

How Is the Trial Designed?

Group I: Diagnostic (FMISO, PET/MRI or PET/CT) Experimental Treatment 5 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

Who Is Running the Clinical Trial?

OHSU Knight Cancer Institute

Lead Sponsor

Trials

239

Recruited

2,089,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Weill Cornell University

Collaborator

Trials

1

Recruited

50+

Oregon Health and Science University

Collaborator

Trials

1,024

Recruited

7,420,000+

Published Research Related to This Trial

The study provides an overview of the development of [18F]fluoromisonidazole ([18F]FMISO) as a radiotracer for imaging hypoxic conditions in tumors, highlighting its importance in assessing oxygen demand in cancer cells for better treatment planning.

A new GMP-compliant method for synthesizing [18F]FMISO achieved a radiochemical yield of 49% in just 48 minutes, with over 99% purity, making it a reliable and efficient option for research and preclinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis of [18F]FMISO, a hypoxia-specific imaging probe for PET, an overview from a radiochemist's perspective. Kniess, T., Zessin, J., Mäding, P., et al.[2023]

In a study involving 14 rats with permanent cerebral ischemia, the PET radiotracer ¹⁸F-FMISO effectively detected hypoxic tissue, showing elevated uptake in the infarcted area for up to 8 hours post-occlusion.

The results indicate that salvageable brain tissue may remain viable for up to 8 hours after ischemia, suggesting that ¹⁸F-FMISO PET could be a valuable tool for assessing the ischemic penumbra in stroke patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of hypoxic tissue dynamics with 18F-FMISO PET in a rat model of permanent cerebral ischemia. Rojas, S., Herance, JR., Abad, S., et al.[2021]

In a study of 23 patients with brain tumors, imaging with the PET tracer 18F-fluoromisonidazole (18F-FMISO) showed that scans taken 4 hours after injection provided more accurate assessments of tumor hypoxia compared to scans taken at 2 hours.

The results indicated that the standardized uptake value (SUV) of gray matter decreased significantly from 2 to 4 hours, while glioblastoma patients exhibited increased SUVmax and tumor-to-normal ratios at the later time point, suggesting better imaging efficacy for hypoxic tumors at 4 hours.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of the scan time point when assessing hypoxia in 18F-fluoromisonidazole PET: 2 vs. 4 h. Kobayashi, K., Manabe, O., Hirata, K., et al.[2021]

In a study of 19 acute ischemic stroke patients, FMISO PET scans were able to predict early infarct growth with a sensitivity of 100% and a specificity of 82%, indicating its potential as a reliable imaging tool.

The results showed that increased FMISO uptake was significantly associated with infarct growth, as 8 out of 10 patients with high FMISO uptake experienced growth, while none of the 9 patients without uptake showed any growth.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

(18)F-fluoromisonidazole (FMISO) Positron Emission Tomography (PET) Predicts Early Infarct Growth in Patients with Acute Ischemic Stroke. Lee, GH., Kim, JS., Oh, SJ., et al.[2017]

Fluoromisonidazole (FMISO) labeled with 18F is a promising imaging agent for detecting hypoxia in various medical conditions, including tumors and cardiovascular diseases, with calculated effective dose equivalents of 0.013 mSv/MBq for men and 0.014 mSv/MBq for women.

The radiation doses from FMISO-PET imaging are comparable to those from other common nuclear medicine tests, suggesting that the associated radiation risks are within acceptable limits, particularly with the urinary bladder wall receiving the highest dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluorine-18-fluoromisonidazole radiation dosimetry in imaging studies. Graham, MM., Peterson, LM., Link, JM., et al.[2016]

Fluorine-18 fluoromisonidazole (FMISO) effectively identifies hypoxic and radioresistant tumors, showing significantly higher uptake in these tumors compared to control tumors, which suggests its potential as a reliable imaging agent in cancer diagnostics.

The study found that FMISO uptake inversely correlates with methionine uptake, indicating that areas of high FMISO uptake correspond to low metabolic activity, while 2-deoxyglucose (2DG) showed a more uniform distribution, suggesting that combining FMISO with other tracers could enhance the prediction of tumor response to radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the distribution of fluorine-18 fluoromisonidazole, deoxyglucose and methionine in tumour tissue. Kubota, K., Tada, M., Yamada, S., et al.[2019]

The study evaluated the pharmacokinetics of fluoromisonidazole (FMISO), a PET imaging agent, in male Sprague-Dawley rats using various doses (0.1, 0.4, 1.6, and 6.4 mg/kg), finding that higher doses resulted in a linear increase in plasma concentration and total area under the curve (AUC), indicating effective dose-response behavior.

Importantly, the elimination half-lives and elimination rate constants were found to be independent of the dose, suggesting that pharmacokinetic properties remain consistent between trace and higher doses, which is crucial for the development of new PET imaging agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Du, J., Zhu, L., Zhou, X., et al.[2019]

A new automated synthesis method for the radiotracer [(18)F]FMISO was developed, achieving a radiochemical yield of over 40% in less than 40 minutes with high purity (over 95%).

This method allows for the efficient production of [(18)F]FMISO, which is important for imaging in hypoxic tumors, potentially improving the availability of this radiotracer for clinical and research applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fully automated one-pot synthesis of [18F]fluoromisonidazole. Tang, G., Wang, M., Tang, X., et al.[2022]

The study demonstrated that 18F-fluoromisonidazole (FMISO) PET imaging can effectively assess tumor hypoxia, showing strong correlations between FMISO metrics and a reference standard using pimonidazole in a rat model with brain tumors.

FMISO's tumor-to-cerebellar uptake (TCmax) and hypoxic fraction were found to be more reliable indicators of tumor hypoxia than conventional maximum standardized uptake values (SUVmax), suggesting that these metrics could improve the accuracy of hypoxia assessment in tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Correlation of Tumor Hypoxia Metrics Derived from 18F-Fluoromisonidazole Positron Emission Tomography and Pimonidazole Fluorescence Images of Optically Cleared Brain Tissue. Scarpelli, ML., Healey, DR., Fuentes, A., et al.[2021]

A study using PET imaging with the hypoxia-binding agent [18F]FMISO found that 97% of tumors in 37 patients exhibited hypoxia, highlighting the prevalence of low oxygen levels in various cancers.

The extent of hypoxia varied significantly among different tumor types and even within regions of the same tumor, emphasizing the need for individualized assessments of tumor oxygenation for better treatment planning.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantifying regional hypoxia in human tumors with positron emission tomography of [18F]fluoromisonidazole: a pretherapy study of 37 patients. Rasey, JS., Koh, WJ., Evans, ML., et al.[2022]

In a study of 35 patients with grade 3 and 4 adult-type diffuse gliomas, 18F-fluoromisonidazole (FMISO) PET imaging showed that IDH-wildtype tumors had significantly higher uptake values compared to IDH-mutant tumors, indicating a potential biomarker for tumor classification.

The combination of FMISO uptake measurements and apparent diffusion coefficient (ADC) values effectively differentiated between IDH-mutant and IDH-wildtype gliomas, with an area under the curve (AUC) of 0.80, suggesting that this imaging approach could enhance diagnostic accuracy for glioma subtypes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of isocitrate dehydrogenase mutation in 2021 world health organization classification grade 3 and 4 glioma adult-type diffuse gliomas with 18F-fluoromisonidazole PET. Wang, Y., Fushimi, Y., Arakawa, Y., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5706929/

18F-Fluoromisonidazole in tumor hypoxia imaging - PMC 18 F-Fluoromisonidazole positron emission tomography ( 18 F-FMISO PET) has been widely used to visualize tumor hypoxia in a comprehensive and noninvasive way.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT01246869

Assessment of Primary and Metastatic Brain Tumor ... Purpose of Study This exploratory clinical study will investigate FMISO (fluoromisonidazole) in patients with (1) newly diagnosed primary malignant brain ...

3. jnm.snmjournals.org jnm.snmjournals.org/content/56/8/1223

18F-Fluoromisonidazole Quantification of Hypoxia in Human ... Survival analysis using 18F-FMISO imaging results from 38 brain tumor patients support the hypothesis that a greater hypoxic tumor burden before ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1878875023006423

18F-Fluoromisonidazole−Positron Emission Tomography ... The aim of this study was to compare FMISO-PET and immunohistochemical findings of tumor oxygenation in the TME of GBM during Bev treatment.

5. aacrjournals.org aacrjournals.org/clincancerres/article/14/9/2623/73526/Regional-Hypoxia-in-Glioblastoma-Multiforme

Regional Hypoxia in Glioblastoma Multiforme Quantified with ... A single field-of-view emission scan from 120 to 140 min postinjection and an attenuation scan (25 min) of the brain with tumor were obtained. The acquired ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4737549/

Tumor Hypoxia Imaging with [F-18] Fluoromisonidazole ... The 73 previously untreated patients with head and neck cancer with follow-up data were analyzed for this study; all had biopsy-proven squamous cell carcinoma ...

7. dctd.cancer.gov dctd.cancer.gov/drug-discovery-development/reagents-materials/imaging-ind-resources/documentation/fmiso-ib.pdf

INVESTIGATOR'S BROCHURE For: [18F]-fluoromisonidazole ([18F]FMISO) is a radiolabeled imaging agent that has been used for investigating tumor hypoxia with positron emission tomography (PET) ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03649880?cond=brain%20cancer&viewType=Table&rank=10

NCT03649880 | Feasibility of FMISO in 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 ...