Imaging tissue derived biomarkers

Biomarkers defintion
1. Biomarkers can be described as measurable and quantifiable indicators of normal physiological function, disease states or of the body's response to therapeutics.
2. The Biomarkers Definition Working Group (2001) classified five different types of biomarker based on function
  1. diagnostic
  2. Prognostic
  3. Predictive
  4. Staging
  5. Surrogate endpoints
3. Biomarkers are present in bodily fluids
  1. Blood and blood fractions (serum, plasma, buffy coat)
  2. Urine
  3. saliva
  4. Tissues
4. National Cancer Institute defines a tumour marker as a substance that may be found in tumour tissue or released from a tumour into the blood or other body fluids
5. Imaging derived biomarkers
  1. Aim: to predict metastatic spread of tumours
    1. which causes the vast majority of cancer related death
  2. the primary tumour is examined for biomarkers which could predict the metastatic event occurring many years later
Overview
1. starting point for imaging process: Tissue microarrays
  1. take small pieces of tumour tissue from individual patients and look for expression of markers across hundreds of tumour specimens simultaneously
2. In vivo imaging used to monitor tumour growth or the response of tumour to treatment
3. New imaging technologies are increasingly being used to understand the in vivo behaviour of cancers
4. Omic approaches provide and overview of biomarkers in cancer
  1. large bottleneck in converting these candidate biomarkers into clinical use
5. Imaging has the ability to take this omic-generated information further, allowing us to see the actual activity and location of the biomarkers in vivo.
Antibody based proteomics (in vitro)
1. forefront of omic technologies
2. Antibodies are useful tools for quantifying protein expression and detecting antigens for biomarkers
3. using bioinformatics, genes of interest are identified and then antibodies are used to profile tissue
  1. s is then combined with vision approaches to develop an assay
4. Antibodies form the basis of tissue microarrays which area platform for high throughput pathology
  1. sections of FFPE taken
    1. looked at under microscope to confirm tissue is cancerous
      1. additional staining is performed to see if the tissue is expressing particular proteins
        Tiny cores are taken from all the tumour samples
        put on master block
        RNA expression analysis is examined with respect to its morphology
  2. Digital pathology used to help this system
    1. major advance from the highly subjective and time consuming method of viewing slides under a microscope
    2. takes a slide, scans it and creates a digital image
    3. uses computer based vision approach rather than relying on pathologist to manually examine it
moves being made toward an in vivo approach
1. advances in clinical imaging are improving how cancer is understood at a systems level and enable doctors to not only locate a tumour but examine its biological processes
2. Imaging systems grouped by
  1. energy used to derive the visual information
    1. X-rays
    2. positrons
    3. photons
    4. sound waves
  2. spatial resolution obtained
    1. macroscopic
      1. widespread use of macroscopic imaging systems that provide anatomical and physiological information
        Computed Tomography (CT)
        Magnetic resonance imaging (MRI)
        ultrasound
    2. microscopic
  3. type of information obtained
    1. anatomical
    2. physiological
    3. cellular
    4. molecular
      1. systems that obtain molecular information are only beginning to be used clinically
        positron emission tomography (PET)
        single-photon emission CT (SPECT)
        fluorescence based imaging
nuclear imaging
1. based on administration and detection of decaying radioisotopes in vivo.
2. These radioisotopes combine with biologically active compounds to form radiopharmaceuticals which target specific molecular events
3. Decaying radioisotopes emit a positron or gamma ray which produce high-energy photons
  1. can be detected using PET or SPECT
    1. PET
      1. a contrast agent or tracer based imaging method
      2. most commonly used tracer is 18F-FDG (flurodeoxyglucose)
        reflects glucose uptake and metabolism
      3. disadvantage:
        PET tracer agents typically have a short half life
        because of this there is a requirement for scanners to be located close to a cyclotron
optical imaging
1. based on photons travelling through tissue and their interactions
2. fluorescence based
  1. fluorescence refers to the property of certain molecules to absorb light at a specific wavelength and emit light of a longer wavelength after a brief interval
  2. discovered in the 19th century
    1. first application was in 1924 when the autofluorescence of endogenous porphyrins were observed in tumour illuminated with ultraviolet light
  3. macroscopic
    1. systems rely on photographic principles to collect images in low light
  4. microscopic
    1. used to examine the activity of cells in biological settings including tumours
    2. possible to analyse multiple cell types at the same time and in solid tissues
    3. Examples
      1. Multiphoton microscopy imaging systems
        yield 3D information from light emitted by fluorescently labelled objects
      2. Intravital multiphoton microscopy
        derives quantitative parameters of intravascular and interstitial cell migration
        cells investigated in lymph nodes, cranial bone marrow, and organs harbouring orthotopic cancers
  5. Tomographic fluorescence systems
    1. reconstruct 3D maps of fluorochromes on the basis of algorithms
    2. enable fluorescent proteins or genetically modified cells to be tracked in vivo
3. non-fluorescence based
In vivo techniques can also be applied to the anti-cancer drug development process
1. Photodynamic therapy is a treatment where a fluorescent photosensitiser (e.g. ADPM) is administered to the patient
2. The drug then preferentially accumulates in tumour cells where it can be illuminated with a light so that it becomes toxic to targeted malignant cells
3. this process has the advantage of only harming toxic cells so it has a low mutagenic potential
4. Example: phototrin

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Imaging tissue derived biomarkers

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	Created by aoife.lacey.1 over 11 years ago