¹⁸F-FMISO or fluoromisonidazole is a radiopharmaceutical used for PET imaging of

hypoxia Hypoxia means a lower than normal level of oxygen, and may refer to: Reduced or insufficient oxygen * Hypoxia (environmental), abnormally low oxygen content of the specific environment * Hypoxia (medical), abnormally low level of oxygen in the tis ...

. It consists of a 2-

nitroimidazole 5-Nitroimidazole is an organic compound with the formula O2NC3H2N2H. The nitro group at position 5 on the imidazole ring is the most common positional isomer. The term nitroimidazole also refers to a class of antibiotics that share similar chemi ...

molecule labelled with the positron-emitter fluorine-18. Hypoxia is considered a negative prognostic marker for many solid tumours, and therefore an agent to detect and quantify it is highly desirable. FMISO was one of the first such agents, after initial synthesis in the late 1980s. It remains among the most popular agents for investigation of hypoxia imaging.

Mechanism

On entering a viable cell, the nitro group of the FMISO nitroimidazole is reduced. In non-hypoxic cells, the reduced FMISO molecule can be oxidised, and therefore diffuses out of the cell to circulate freely and ultimately be excreted. In hypoxic tumour cells however this oxidation cannot take place and the FMISO molecules accumulate. Their location can then be

quantitatively Quantitative research is a research strategy that focuses on quantifying the collection and analysis of data. It is formed from a deductive approach where emphasis is placed on the testing of theory, shaped by empiricist and positivist philosop ...

imaged using

positron emission tomography Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in Metabolism, metabolic processes, and in other physiological activities including bl ...

Clinical use

Large scale

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...

s with FMISO have not been carried out, however there is some evidence from small-scale early-stage imaging trials that PET-measured hypoxia (using FMISO, and the alternative radiotracer FAZA) is linked to

overall survival Survival rate is a part of survival analysis. It is the proportion of people in a study or treatment group still alive at a given period of time after diagnosis. It is a method of describing prognosis in certain disease conditions, and can be use ...

and loco-regional control in

head and neck cancer Head and neck cancer develops from tissues in the lip and oral cavity (mouth), larynx (throat), salivary glands, nose, sinuses or the skin of the face. The most common types of head and neck cancers occur in the lip, mouth, and larynx. Symptoms ...

patients. Similar correlations have been found in other cancers, including

breast cancer Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a re ...

and

brain tumour A brain tumor occurs when abnormal cells form within the brain. There are two main types of tumors: malignant tumors and benign (non-cancerous) tumors. These can be further classified as primary tumors, which start within the brain, and secondary ...

s. Direct impacts on patient care has not yet been conclusively demonstrated however. The use of hypoxia imaging to guide

radiotherapy Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radia ...

treatments is an area of active research. Despite some positive early results further research is required to characterise the

specificity and sensitivity In medicine and statistics, sensitivity and specificity mathematically describe the accuracy of a test that reports the presence or absence of a medical condition. If individuals who have the condition are considered "positive" and those who do ...

of FMISO, and exactly how hypoxia levels should influence

treatment planning In radiotherapy, radiation treatment planning (RTP) is the process in which a team consisting of radiation oncologists, radiation therapist, medical physicists and medical dosimetrists plan the appropriate external beam radiotherapy or internal b ...

decisions. Similarly, hypoxia imaging could be used to screen patients before the prescription of hypoxic guided drugs. It may also be useful as a post-treatment measure of effectiveness for both radiotherapy and

chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...

. Outside of

oncology Oncology is a branch of medicine that deals with the study, treatment, diagnosis and prevention of cancer. A medical professional who practices oncology is an ''oncologist''. The name's etymological origin is the Greek word ὄγκος (''ó ...

, there is interest in cardiac hypoxia imaging. FMISO has had limited interest for this purpose, in part due to low target-to-background contrast and long injection to imaging delays (due to slow blood clearance) requiring high injected activities.

References

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External links

18F-Fluoromisonidazole
Molecular Imaging and Contrast Agent Database (MICAD) PET radiotracers Nitroimidazoles