Monitoring: Imaging Flashcards
What is PET used for (broadly)?
Molecular imaging by Positron Emission Tomography (PET) allows for in vivo visualization of immune targets at picomolar level. By synthesis of a PET tracer that binds to the target of interest, the target can be visualized in vivo: in animal models and in patients.
What is the principle of PET at tissue level?
PET tracer is injected into a blood vessel. The permeability of the blood vessel at the site of inflammation is larger than normal, so the PET tracer can get into the inflamed tissue where it can bind its receptors on the immune target of interest. Since the tracer is combined with a radionucleotide, it will be visible for the PET camera.
What are developments in applications of immune target imaging by PET in rheumatology?
• Early diagnostics of rheumatic diseases
Early therapy monitoring to predict the outcome of treatment
• Development of personalized treatment by in vivo identification of dominant immune profile in the individual patient
• Pathogenetic studies: in vivo investigation of target expression and imaging-guided tissue analyses
• Support of development of new therapeutic drugs by radiolabeling of the drug pharmacokinetics and dynamic studies.
Why are macrophages important in rheumatoid arthritis?
- They are present from the early development of RA onwards
- They relate to therapy efficacy
- They are systemically involved in inflammation
Macrophages are biomarkers for:
•Disease activity: can be used for early diagnosis
•Response to treatment: can be used for monitoring
What is the role of B-cells in rheumatoid arthritis?
They involve plasma cells that synthesize auto-Abs that play a major pathogenetic role like IgM-RF and anti-CCP.
B-cells also secrete cytokines that activate macrophages, fibroblasts, and (directly or indirectly) the osteoclasts that damage the bone.
What is spondyloarthritis?
A group of rheumatic diseases with inflammation in the spine and sacroiliac joints (pelvis). The spine starts looking like bamboo and there is ankylosis of sacroiliac joints.
What is a tool for diagnostics and monitoring spondyloarthritis?
F-18-fluoride is a PET tracer that has an affinity to deposit at areas where the bone is newly mineralizing. It is an imaging marker for new bone formation and indirectly for osteoblast activity.
Why is fibronectin expression in the rheumatoid arthritis synovium a target for therapy?
Fibronectin expression is associated with fibroblast activity and with angiogenesis in RA synovium. Both present since early disease.
- Imaging of targeted delivery of IL-10 is possible by binding it to fibronectin in RA.
- F8IL10 is a fusion of anti-inflammatory cytokine IL-10 to the antibody fragment. F8 binds to ED-A of fibronectin to allow targeted delivery to RA joints. By labeling F8IL10, in vivo biodistribution of the therapeutic agent can be imaged.
- Fibronectin ED-A stainings of spleen and liver in arthritic rats showed significantly higher uptake of fibronectin in spleen and liver in RA rats compared to healthy rats. Most likely effect of the systemic inflammation.
What are the properties of FDG-18F?
Binds glucose transporter and is used for investigation of glucose metabolism. Accumulates at any site that is metabolically active (mainly macrophages). Highly sensitive, but less specific.
What are the properties of (R)-PK11195-11C?
Binds to translocator protein (TSPO) from the peripheral benzodiazepine receptor and is used for neuro-inflammation/RA (because it might also be activated on macrophages there).
What are the properties of PEG-folate-18F?
Binds to Folate receptor beta (highly expressed on activated macrophages in RA) and is used for RA and atherosclerosis.
