KW seminar: Molecular imaging Flashcards
What is molecular imaging?
Molecular imaging encompasses a variety of imaging techniques that rely on the use of exogenously added specific probes (tracers/contrast agents) to target and detect desired cellular and molecular processes in a living organism.
Very roughly, what different techniques are there?
- Ultrasound
- Photo acoustic microscopy
- Optical coherence tomography
- Magnetic force microscopy
What is nuclear imaging?
Nuclear imaging is a method of producing images by detecting radiation from different parts of the body after a radioactive probe is given to the patient. The images are digitally generated on a computer and transferred to a nuclear medicine physician, who interprets the images to make a diagnosis
Also called “endoradiology”: because (it records radiation emitting from within the body rather than radiation that is generated by external sources like X-rays. In addition, nuclear medicine scans differ from radiology, as the emphasis is not on imaging anatomy, but on the function.
What are the two most common forms of nuclear imaging?
Single photon emission computed tomography (SPECT) and positron emission tomography (PET)
What is optical imaging?
Medical optical imaging is the use of light as an investigational imaging technique for medical applications. The probe that could be used for this is fluorescent dye
What are some examples of optical imaging?
Optical microscopy, spectroscopy, endoscopy, scanning laser ophthalmoscopy, laser Doppler imaging, and optical coherence tomography.
The lecturer doesn’t name this, but I think he means microscopy when referring to optical imaging. All the other forms you do not have to study
Explain what the sensitivity, resolution and depth is of nuclear imaging (probe: radionuclide)
Sensitivity: high
Resolution: moderate
Depth: whole body
Explain what the sensitivity, resolution and depth is of optical imaging (probe: fluorescent dye)
Sensitivity: high
Resolutation: high
Depth: superficial
Explain what the sensitivity, resolution and depth is of MRI imaging (probe: paramagnetic agent)
Sensitivity: poor
Resolution: high
Depth: whole body
For an overview and comparison of the different molecular imaging, see this figure
Okay
What two molecular imaging are the best options for molecular imaging, due to picomolar sensitivity?
Nuclear and optical imaging (MRI has a poor sensitivity)
What two forms of molecular imaging are best for examining the whole body?
Nuclear and MRI imaging (optical imaging is very superficial, and you need a thin slice of tissue to study under the microscope)
What probe is used in a PET-scan?
A sugar, called F-18 FDG
What shift is seen in the clinic regarding imaging?
That, as we learn more about diseases, we are becoming more aware that this happens on cellular, and even genetic level. Therefore we are using molecular imaging nowadays more than e.g. X-rays
Molecular imaging fills the gap between molecular ___, molecular ___ and molecular ___ ___
Molecular imaging fills the gap between molecular biology, molecular diagnosis and molecular targeted therapy
Molecular imaging of targets and drugs. To keep the health care system affordable
Fill in:
In biology, ___ of disease as well as ___ drugs have to be understood better.
Drug design and development should become more efficient and cheaper: selection of ___ drugs at an early stage, with less patients in trials, showing the distinguished properties of the drug.
(Drug) treatment should become more ____.
In biology, targets of disease as well as targeted drugs have to be understood better.
Drug design and development should become more efficient and cheaper: selection of high potential drugs at an early stage, with less patients in trials, showing the distinguished properties of the drug.
(Drug) treatment should become more “personalized/precise”.
True/false: Drug development is too expensive
True
Development costs of drug to market: > 1 billion dollar
Drug development is not efficient enough. About 65% of the trials fail at a certain phase. Which phase is this?
Phase II of clinical trials
Drug development is not efficient enough. How many % of drugs in clinical devleopment reach the market?
About 10% of drugs in clinical development reaches the market
We’ve seen that 10% of the drugs in clinical trials reach the market. However these drugs are not effective enough. Why?
Because often only 40% of the patients benefit from the drug. Imagine that a drug sales worldwide yearly ~1000 billion euro’s. This means that 600 billion is spent in vain because the patients do not benefit
There has been a change in the categories of drugs (size). What is this change?
From small chemical molecules to a diversity of biologicals.
Why is there a change from small chemical molecules to a diversity of biologicals?
Becuase biologicals have a much longer half-time (e.g. peptides hav a half-life of 2 hours before they are destroyed by the liver, monoclonal antibodies 120+ hours)
What are the characteristics of next generation targeted biologicals?
More potent, multiple specificities and (immune) functions
What are some examples of next generation targeted biologicals?
For illustration
- Antibody drug conjugates (ADCs)
- Immune checkpoint inhibiting antibodies (ICIs)
- Fusion antibodies, e.g. immunocytokines
- Bi- and multispecific antibodies
- Antibody fragments, antibody-like scaffolds
- Polynucleotides
- Nanoparticles
- Cells
Where is the UMC imaging center?
At the zuidas, on the VU campus
At what three ‘stages’ of the care cycle during the treatment of a cancer patient is imaging used and why?
- Diagnose/stratification: what/where/how is the disease
-
Image-guided therapy: Is the disease accurately targeted?
- Surgery, radiotherapy, chemotherapy, immunotherapy and nanotherapy
- Response monitoring: is the treatment effective?
Probes and positron emitters for PET imaging. Fill in:
- Fast kinetics targeting probes are long/short-lived radionuclides
- Slow kinetics targeting probes are long/short-lived radionuclides
- Fast kinetics targeting probes are short-lived radionuclides
- Slow kinetics targeting probes are long-lived radionuclides
What is the potential impact of drug imaging?
- Assessment of expression and accessibility of target (also in e.g. brain).
- Assessment of pharmacokinetics and biodistribution of drug.
- Whole body, non-invasive, quantitative and longitudinal.
- Confirmation of selective disease targeting – anticipate toxicity.
- Optimization of drug dose: avoiding “sinks”, homogeneous targeting.
- Identification of patients group with highest chance of benefit.
- Individualization of therapy (companion – complementary diagnostics).
- Mechanism of action: showing distinguished properties of a drug.
How can 89-Zr labeling be used in the clinic?
It can be used for drug targeting. For example, you bind 89ZR to rituximab so that it binds specifically to tumor cells
Can 89Zr-trastuzumab also be used to detect metastasis?
Yes, although not seen in the PET scan (left image), the 89-Zr-trastuzumab did show metastasis in the body (middle figure), which were later shown atanomicall (right figure)
Since trastuzumab is very selective, and has shown to point out metastasis not only in mice but also in humans (see figure). How can this further be usedin the clinic?
It allows the use as an Antibody-drug conjugate (ADC). You can bind a drug to the marker, so that the drug only binds to the tumor
What are the advantages of using both radiochemistry and imaging in ADC development?
- controlled coupling
- unimpaired MAb integrity
- and antigen binding
- stable in vitro and in vivo
- optimal tumor targeting
How can platinum (Lx) be used in the clinic?
As a 2-sided adhesive, the (toxic) drug can bind on one side, and an antibody on the other
This is called linker technology
What efficacy does the linker technology show?
Improved efficacy
What did we learn from alleviating PD1/PD-L1 mediated inhibition?
As an example
We understood the immune system
What results were found with use of molecular imaging with targeting reumatoid artritis?
As an example
With inhibition of 89Zr-rituximab (CD20/B cells), the disease could clearly be shown and targeted at the same time
How could you evade the problems of a drug in a deep brain tumor, which has a impossible location to operate, and many drugs don’t pass the blood-brain-barrier?
Not study material
By using a intra-arterial (IA) injection with a blood-brain-barrier opening
See the red bars which are much higher than the blue/grey
Thus with use of the PET scan, 89Zr-antibody gives access to the brain. In what other diseases besides brain tumors could this treatment be developed?
Not study material
All brain diseases, Alzheimer’s, Parkinson’s, MS
