Fluorescence Molecular Tomography (FMT)

We use a multi-channel PerkinElmer (formerly Visen) FMT system for near-infrared (NIR) based three-dimensional whole body, fluorescence imaging in mice.

FMT technology enables quantitative imaging of the fluorescent probe, or marker concentration to the picomolar level with no tissue depth limitation. The increasing assortment of commercially-available NIR probes provides greater and more versatile access to fluorescent-imaging biomarkers that can be used to assess disease progression and drug response at the molecular, cellular and target levels. FMT can also be used as a discovery screening tool for assessing biologics biodistribution rapidly and cost effectively in the whole body.

Capabilities and Applications

  • A variety of blood-pooling NIR probes of varying sizes can be used for imaging vessel permeability, blood flow and vessel density. Applications include angiogenesis and tumor burden tracking.

  • NIR probes can be targeted to a variety of cell surface markers and receptors to enable imaging of target expression and modulation. Examples of commercially-available probes include those targeted to:

    • Hydroxyapatite: Hydroxyapatite is a metabolite involved in bone turnover. Applications include imaging of bone metastasis, bone degradation in arthritis and osteoporosis.
    • αvβ3: The αvβ3 integrin is involved in vessel formation. αvβ3-targeted probes, such as IntegriSense, (PerkinElmer; co-developed by Merck) allow the imaging of new vessel formation and tumor burden.
    • Hypoxia: The HypoxiSense probe (PerkinElmer) allows three-dimensional, FMT-based imaging of tissue hypoxia through targeting to the carbonic anhydrase 9 (CA IX) protein. This protein increases in hypoxic regions within many tumors, especially in cervical, colorectal, non-small cell lung tumors.
    • Annexin/Apoptosis: The Annexin Vivo contrast agent (PerkinElmer) selectively binds phosphatidylserine exposed in the outer leaflet of the cell membrane during the early stages of apoptosis. This enables FMT-based imaging of apoptosis.
    • Her2: Her2 is commonly over-expressed in human breast cancer and is the target of many breast cancer therapeutics. A Her2-targeted probe can be used for imaging of Her2 expression and therapeutic knockdown.

  • NIR-activated probes provide the opportunity to image the modulation of target-specific molecules. These probes are in a quiescent or quenched fluorescence state prior to activation and fluorescent activity. Commercially-available, activatable NIR probes exist for a variety of target molecules including:

    • Cathepsins: Cathepsins are upregulated in a variety of disease states including inflammation and cancer. These probes can quantify the early and specific aspects of rheumatoid arthritis and other inflammatory diseases. They can also be used for tumor-burden tracking since tumors broadly produce high levels of cathepsins. Pan-cathepsin probes are available (e.g. ProSense) as well as probes specific to Cathepsin B (e.g. CatB FAST) and Cathepsin K (e.g. CatK FAST). Notably, Cathepsin K is commonly upregulated in the osteoblastic components of bone degradation and can be used to assess therapeutics targeted against this process in bone disease. 
    • Matrix metalloproteinases (MMPs): MMPs are active in inflammation diseases and cancer. MMP-activatable fluorescent probes can be used both for quantifying the early and mechanistic aspects of rheumatoid arthritis and other inflammatory diseases. They can also be used for tumor burden tracking since tumors commonly produce high levels of MMPs.
    • Neutrophil elastase: Neutrophil elastase is a protease involved in a variety of indications including acute lung injury, acute respiratory distress syndrome, as well as many other inflammatory processes such as emphysema, cystic fibrosis, COPD, wound healing, rheumatoid arthritis, and ischemia-reperfusion.

  • Standard labeling techniques using a variety of commercially-available, NIR fluorophore kits enable three-dimensional, FMT-based imaging of biodistribution. This technique is particularly well suited to characterization of pharmacokinetics, pharmacodynamics, clearance pathways, and targeting of biomolecules such as proteins, peptides, and antibodies. FMT imaging provides a high-efficiency, low-cost method for discovery stage screening and later stage decision making for therapeutic biologics.