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

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. ^{1 2 3 4 5}

Is 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. ^{1 2 6 7 8}

How 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. ^{2 6 9 10 11}

Research Team

Ramon Barajas

Principal Investigator

OHSU Knight Cancer Institute

Eligibility 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

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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]

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]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Comparison of the distribution of fluorine-18 fluoromisonidazole, deoxyglucose and methionine in tumour tissue. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Synthesis of [18F]FMISO, a hypoxia-specific imaging probe for PET, an overview from a radiochemist's perspective. [2023]

3. Switzerland 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. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Quantifying regional hypoxia in human tumors with positron emission tomography of [18F]fluoromisonidazole: a pretherapy study of 37 patients. [2022]

5. Japan 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. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Evaluation of hypoxic tissue dynamics with 18F-FMISO PET in a rat model of permanent cerebral ischemia. [2021]

7. England 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. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Fully automated one-pot synthesis of [18F]fluoromisonidazole. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

Influence of the scan time point when assessing hypoxia in 18F-fluoromisonidazole PET: 2 vs. 4 h. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

(18)F-fluoromisonidazole (FMISO) Positron Emission Tomography (PET) Predicts Early Infarct Growth in Patients with Acute Ischemic Stroke. [2017]

11. United States pubmed.ncbi.nlm.nih.gov

Fluorine-18-fluoromisonidazole radiation dosimetry in imaging studies. [2016]