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Questions and Answers
What is a critical feature of a reporter gene probe?
What is a critical feature of a reporter gene probe?
Which of the following statements about optical imaging is true?
Which of the following statements about optical imaging is true?
What is a significant advantage of ultrasound imaging compared to optical imaging?
What is a significant advantage of ultrasound imaging compared to optical imaging?
Which of the following accurately describes the resolution of optical imaging?
Which of the following accurately describes the resolution of optical imaging?
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What limitation does optical imaging face in terms of tissue penetration?
What limitation does optical imaging face in terms of tissue penetration?
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How does ultrasound imaging produce an image?
How does ultrasound imaging produce an image?
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Which application is not typically associated with optical imaging?
Which application is not typically associated with optical imaging?
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What is a primary disadvantage of ultrasound compared to optical imaging?
What is a primary disadvantage of ultrasound compared to optical imaging?
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What defines the specific activity of a radionuclide?
What defines the specific activity of a radionuclide?
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Which statement is true regarding effective half-life?
Which statement is true regarding effective half-life?
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How is the radioactive decay process described?
How is the radioactive decay process described?
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What is the relationship between physical half-life and biological half-life when calculating effective half-life?
What is the relationship between physical half-life and biological half-life when calculating effective half-life?
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What does radioactivity measure?
What does radioactivity measure?
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Which type of decay involves the emission of an electron?
Which type of decay involves the emission of an electron?
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What is the maximum allowable time from the production of a radionuclide to its application?
What is the maximum allowable time from the production of a radionuclide to its application?
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In the equation for calculating effective half-life, what does the term 2 signify?
In the equation for calculating effective half-life, what does the term 2 signify?
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What is the half-life of 82Rb+ used in perfusion imaging?
What is the half-life of 82Rb+ used in perfusion imaging?
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Which property of 82Rb+ contributes to its high extraction fraction in the myocardium?
Which property of 82Rb+ contributes to its high extraction fraction in the myocardium?
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What is the assumed uptake mechanism for [13N]NH3 in myocardial imaging?
What is the assumed uptake mechanism for [13N]NH3 in myocardial imaging?
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Which of the following tracers has a shorter physical half-life than 82Rb+?
Which of the following tracers has a shorter physical half-life than 82Rb+?
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Which tracer is produced by a generator?
Which tracer is produced by a generator?
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What is the metabolic fate of ammonium from [13N]NH3 in cells?
What is the metabolic fate of ammonium from [13N]NH3 in cells?
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Which perfusion tracer provides high image resolution due to its β+-Energy level?
Which perfusion tracer provides high image resolution due to its β+-Energy level?
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What is a key feature of [15O]H2O in perfusion imaging?
What is a key feature of [15O]H2O in perfusion imaging?
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Which mechanism of accumulation involves the incorporation of antibodies to target specific antigens?
Which mechanism of accumulation involves the incorporation of antibodies to target specific antigens?
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What is the most stable oxidation state for Technetium-99m?
What is the most stable oxidation state for Technetium-99m?
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Which of the following is NOT a mechanism of accumulation for a Tc-99m radiotracer?
Which of the following is NOT a mechanism of accumulation for a Tc-99m radiotracer?
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Which Tc-99m radiopharmaceutical is used for liver scintigraphy?
Which Tc-99m radiopharmaceutical is used for liver scintigraphy?
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What is the required energy emitted during the decay of Technetium-99m?
What is the required energy emitted during the decay of Technetium-99m?
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Which oxidation state of Technetium-99m is involved in penetrating the blood-brain barrier?
Which oxidation state of Technetium-99m is involved in penetrating the blood-brain barrier?
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What is the half-life of the 99Mo/99mTc generator?
What is the half-life of the 99Mo/99mTc generator?
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In terms of complex geometry, what primarily influences the structures formed by Technetium-99m?
In terms of complex geometry, what primarily influences the structures formed by Technetium-99m?
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What type of Tc-99m radiopharmaceutical can be used for thyroid imaging?
What type of Tc-99m radiopharmaceutical can be used for thyroid imaging?
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Which mechanism helps in the uptake of Tc-99m radiotracers through the action of lipophilic groups?
Which mechanism helps in the uptake of Tc-99m radiotracers through the action of lipophilic groups?
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What is the half-life of the tracer [18F]Flurpiridaz?
What is the half-life of the tracer [18F]Flurpiridaz?
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Which uptake mechanism is involved with [18F]Flurpiridaz?
Which uptake mechanism is involved with [18F]Flurpiridaz?
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What is a key property of an ideal tracer for measuring myocardial blood flow?
What is a key property of an ideal tracer for measuring myocardial blood flow?
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Why is 18F-FDG considered unsuitable for myocardial blood flow measurement?
Why is 18F-FDG considered unsuitable for myocardial blood flow measurement?
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What makes [15O]H2O the gold standard for quantifying myocardial blood flow?
What makes [15O]H2O the gold standard for quantifying myocardial blood flow?
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What is a noteworthy characteristic of the uptake mechanism of [18F]Flurpiridaz?
What is a noteworthy characteristic of the uptake mechanism of [18F]Flurpiridaz?
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How is imaging quality for tracers assessed in myocardial blood flow measurement?
How is imaging quality for tracers assessed in myocardial blood flow measurement?
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What significant impact does revascularization have on patients with myocardial viability?
What significant impact does revascularization have on patients with myocardial viability?
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What is the primary role of Carbidopa in Parkinson’s disease treatment?
What is the primary role of Carbidopa in Parkinson’s disease treatment?
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In which context is [11C]Raclopride used?
In which context is [11C]Raclopride used?
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Which radiolabeled compound is best associated with dopamine transporter imaging?
Which radiolabeled compound is best associated with dopamine transporter imaging?
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What characterizes the SPECT findings in idiopathic Parkinson's disease?
What characterizes the SPECT findings in idiopathic Parkinson's disease?
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How is cerebral glucose metabolism related to neuronal function?
How is cerebral glucose metabolism related to neuronal function?
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Which statement is true about the uptake of [18F]FDG in the brain?
Which statement is true about the uptake of [18F]FDG in the brain?
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What change is observed in D2 receptor availability after prolonged drug detoxification?
What change is observed in D2 receptor availability after prolonged drug detoxification?
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What modification was made to the cocaine structure to stabilize its radiolabeled tracers?
What modification was made to the cocaine structure to stabilize its radiolabeled tracers?
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Study Notes
Molecular Imaging
- Molecular imaging is an intersection of molecular biology and medicine, enabling the visualization of physiological processes and cellular functions
- Molecular imaging techniques combine structural information and molecular signatures
- It provides relevant information for drug discovery and development
Biomarker
- A biomarker is a laboratory measurement that can reflect the activity of a disease process
- It can predict drug efficacy but might not always predict therapeutic outcome
- It should provide information about a critical path in the disease's development
Imaging principles
- Imaging comprises: Probe → Matter interaction → Detection → Image production
- Imaging scale: size (nm → m), time (ms → y)
General Concepts in Molecular Imaging
- Morphological imaging: Identifies the structure of a biological system
- Functional imaging: Identifies cellular signatures and events in living systems
- Hybrid imaging: Combines morphological and functional imaging
- Label-free/Probe-free Imaging: Target-unspecific, predominantly for morphological imaging
- Probe-based imaging: Target-specific, predominantly for functional imaging
Molecular Probe design
- Reporter probes, methods, and reporter genes
Direct (targeted) reporter probes
- Label part: Radionuclide, Fluorescent molecule, Paramagnetic metal complex or Air bubble
- Pharmacophore: small molecule, peptides, antibody, oligonucleotide, macromolecule, etc.
- Activatable reporter probes involve a non-active substrate, activated upon binding the target (i.e., FRET, BRET)
Direct method
- Labelled drug lead: Structurally identical or very similar, pharmacological and pharmacokinetic characteristics similar, shares the same target (e.g., [11C]-Erlotinib)
Indirect/surrogate method(s)
- Surrogate probe: Structurally different but competes for same target (e.g., Eliprodil → [11C]NB1)
- Surrogate probe and surrogate target: Structurally unrelated, different target(i.e., [18F]FDG (Glut1) → Tyrosin kinase receptor)
Reporter gene
- Foreign gene is introduced into cell genome, a stimulus expresses the gene, detected by reporter probe or the protein's own signal.
Optical imaging
- Probe: Photon (λ = 300-800 nm)
- Matter interaction: Absorption, penetration, scattering
- Modalities: Fluor-, Biolumin-, Phosphorescence
- Resolution: 1-5/1 mm
- Chemical Probe: Near-infrared fluorochromes (NIR)
- Application: Cellular and pre-clinical imaging
- Advantages: High sensitivity (10-⁹ M), functional imaging, no ionizing radiation.
- Limitations: Only pre-clinical, low penetration in tissue, high absorption in tissue, mostly 2D
- Function: Fluorophore excitation, relaxation, fluorescence after excitation (e.g., FRET, BRET)
Ultrasound
- Probe: Radiofrequency wave (λ < 1.5 mm)
- Matter interaction: Reflection
- Modalities: Ultrasonography
- Resolution: 50-100 μm
- Chemical Probe: None or microbubbles
- Application: Vascular and interventional imaging, pregnancy, thoracentesis
- Advantages: High spatial resolution, inexpensive, 4D, no ionizing radiation, fast, non-invasive.
- Limitations: Low sensitivity (10-⁴ M), limited penetration depth, predominantly morphological imaging, inability to image through air pockets or bone, quality depends on skill.
- Function: Wave reflection and distance measurement
MRI
- Probe: Radiofrequency waves (non-ionizing)
- Matter interaction: Nuclear spin transition
- Modalities: Magnetic resonance imaging (MRI), spectroscopy (MRS), functional MRI (fMRI), hyperpolarized
- Resolution: 50-100 μm
- Chemical Probe: None (H₂O in the body) or paramagnetic contrast agents (Gd-, Fe-complex)
- Application: Neurology, oncology, cardiology, tumor, brain, spine, musculoskeletal system
- Advantages: Excellent soft tissue contrast, high spatial resolution, non-invasive.
- Limitations: Low sensitivity (10-⁴ M), poor hard matter contrast, predominantly morphological imaging. expensive, long scan times, strong magnetic field (e.g. contraindicated for patients with pacemakers).
X-ray, CT
- Probe: X-ray photons
- Matter interaction: Transmission, absorption, scatter
- Modalities: X-ray (2D), computer tomography (CT, 3D), phase-contrast X-ray/CT
- Resolution: 10-50 μm
- Chemical Probe: None or contrast agents
- Application: Trauma, oncology, cardiology etc; bone trauma, infarction, tumors, calcification; cardiac, angiography, fibrosis, pulmonary embolism
- Advantages: Highest spatial resolution, inexpensive, fast, high contrast resolution, non-invasive.
- Limitations: Ionizing radiation (dose), poor soft tissue contrast, low sensitivity (10³ M), morphological imaging, radiation exposure
- Examples of probes: Compounds containing heavier elements (I, Ba, Th)
PET, SPECT
- PET: Positron emission tomography
- SPECT: Single photon emission computed tomography
- Probe: y-ray, positron → y-ray
- Matter interaction: Transmission, absorption (annihilation), scattering
- Modalities: Positron emission tomography (PET), Single photon emission computer tomography (SPECT), scintigraphy (2D)
- Resolution: 5-10 mm
- Chemical Probe: Radiotracers, radiopharmaceuticals (radiolabelled molecules)
- Application: Neurology, oncology, cardiology, drug development, animals, various organs, function (e.g., liver, kidney, thyroid, heart, lung)
- Advantages: Highest sensitivity, high functioning imaging, microdosing.
- Limitations: Ionizing radiation (dose), very expensive. poor spatial resolution
- Typical probes: Probes are needed and essential, radiolabelled molecules
Radiopharmacy
- Radiopharmacy: Preparation, characterization, and QC of radioactive materials for human use; molecular imaging, and radionuclide therapy
- Radiopharmaceutical: Medicinal product containing a chemical/biological part with a radionuclide/isotope. No pharmacological effect.
- Radioactive decay: Random process of unstable nuclei, release excess energy in form of ionizing radiation
- Radioactivity (A): Nuclear disintegrations per second Specific activity (Aspec): Radioactivity per unit mass of a radionuclide
- Half-life (T½): Time for a quantity of radionuclide to decrease to half its original quantity
- Effective half-life (effT½): Reduced lifetime of a radiopharmaceutical in an organ
Types of decay
- Chart, range, shielding, Crossfire effect
SUV
- Factor determining tracer kinetics, Compartment models (all types), Reverse and irreversible binding, How to choose a model
Standard Uptake Value
- SUV = Bq in tissue or organs / (Bq injected dose/g body weight)
- SUV >1 in region of interest → heterogeneous tissues distribution; <1 → regions lower radioisotope concentrations
- Kinetics is needed to determine tracer kinetics, compartment model, and binding (reversible or irreversible)
Compartment model curves
- Reference tissue curve
- Specific and non-specific binding
Types of radiation
- Ionizing radiation, LET, Gy and Sv, WR and WT
Dosimetry
- Absorbed dose, Equivalent dose, Effective dose
Radiation, dose-effects and limitations
Internal Radiation Dosimetry
Radiolabelling concepts Isotope*(Bio)isosteres
- Type of chemistry - Covalent bonds: direct labelling of radiocarbon or radiohalogens, 'organic' radionuclides
- Type of chemistry - Coordinative bonds: labelling using metal chelators of peptides or proteins or radiometal labelling.
Quality Control of Radiopharmaceuticals
- Radionuclide purity (isotopic purity): Fraction of total radioactivity coming from desired radionuclide.
- Radiochemical purity: Fraction of total radioactivity coming from desired chemical form (e.g., [¹⁸F]FDOPA, [⁹⁹mTcO₄⁻]), determined by HPLC or TLC.
- Chemical purity: Absence of undesired contaminants (e.g., Al³⁺).
- Biological purity: Absence of pyrogens (e.g., endotoxins) and sterility (absence of microorganism, e.g., bacteria).
General Composition of a Kit
- Components: Active component/ligand, reducing agent, auxiliary components, auxiliary ligand
- Possible mechanisms of accumulation of TC-99m Radiotracer: Passive transport/diffusion, lons transport, Antigen-antibody binding, Adsorption/Chemisorption, Sequestering of cells, Metabolic trapping.
99mTc-Chemistry
- Selected Tc-99m Radiopharmaceuticals
- 99mTc (and 186/188Re): Structure, Complex geometry, Production
[99mTc]Tc-Sestamibi, [99mTc]Tetrofosmin
[99mTc]MAG3, [99mTc]MDP, [99mTc]Medronate
[99mTc/186Re]-MDP, [99mTc/186Re]-EDTMP, [89Sr/223Ra]-analogues
[11C]Methylation reactions
[11C]CO2 reactions
F-18 production
- Reaction summary: Aliphatic nucleophilic 18F-substitution, Aromatic nucleophilic 18F-substitution
Aliphatic Nucleophilic F-substitution
Aromatic Nucleophilic F-substitution
Neurology (Brain cuts)
- Biological targets: AADC, D2 receptors, DAT transporter, misfolded proteins.
- Metabolism: glucose metabolism trace [¹⁸F]FDG.
- Perfusion: [¹⁵O]H₂O, ⁹⁹mTc-HMPAO, ⁹⁹mTc-ECD, ⁹⁹mTcO₄⁻.
Neurology (Dopaminergic System)
- Dopamine synthesis: ¹⁸F]FDOPA
- D2 Receptor: ¹¹C]Raclopride
Neurology (Alzheimer's Disease)
- Misfolded proteins: Beta-amyloid, Tau
- Amyloid PET Tracers: ¹⁸F]flutemetamol, ¹¹C]PIB, ¹⁸F]Florbetapir
- Tau PET Tracers: ¹⁸F]RO948, ¹⁸F]FTP, ¹⁸F]Flortaucipir
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Description
Test your knowledge on radiology and various imaging techniques, including optical imaging and ultrasound. This quiz covers critical concepts such as the features of reporter gene probes, resolution, limitations, and applications of different imaging modalities.