Radiology and Imaging Techniques Quiz

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

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.