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