Radionuclide Imaging , Mechanisms of Administration and Localization of Radiopharmaceuticals

Radionuclide Imaging

• Radionuclide imaging is part of the wider discipline of nuclear medicine.
• Nuclear medicine is based on the notion of a 'tracer'. A tracer is something that is introduced into a system to gain information about the system’s function.
• It is chosen such that it does not disturb the system and, ideally, it has properties that allow it to be detected outside the system.
• In nuclear medicine, the system is the human body and the tracer is the radiopharmaceutical.
• The tracer's fate within the body is determined by physiological processes. It may be monitored by detecting gamma radiation emitted from the body. This is known as 'in vivo' nuclear medicine , Alternatively, gamma or beta radiation may be detected in tissue or fluid samples taken from the body ('in vitro' nuclear medicine).
• For a radiopharmaceutical to be an effective diagnostic tracer, it should not have any real pharmaceutical (drug) effect.

• Radionuclide imaging differs from radiography with x-rays in several important respects:-

1. It utilizes gamma radiation from a radioactive substance.
2. The radioactive substance (in the form of a radiopharmaceutical) is administered to the patient (i.e. it is introduced into the patient's body) so that the patient becomes the source of radiation.
3. Images are created using equipment known as a gamma camera.
4. Image contrast is largely determined by organ uptake (which depends on physiological function) rather than physical factors such as density and average atomic number.
5. The radiation dose to the patient is largely determined by the nature and quantity (activity) of the radiopharmaceutical

Methods of Administration of Radiopharmaceuticals :-

Intravenous injection

• Intravenous injection is used for the majority of nuclear medicine studies. Typically, IV injections into the antecubital fossa are used either directly or via a Venflon??(18 or 20 gauge).
• If using a Venflon, sterile saline must be used as a flush.
• For paediatric studies, a butterfly needle, typically 23-25 gauge, and 3-way tap may be used. The injection site is usually the dorsum of the hand or foot as these veins are more accessible. Sterile saline must be used as a flush.

Inhalation

• Inhaled radiopharmaceuticals are used almost exclusively for lung ventilation imaging.

1. Aerosols :

- Aerosols can be inhaled by the patient for deposition of a radiopharmaceutical within the lungs.????

- The ideal diameter of droplets for maximum penetration of the small airways and deposition within the lungs is ~0.5 μm.????

- Liquid aerosols can be produced in a number of ways, including jet nebulisation, ultrasound and the use of propellants.????

- A solid particle aerosol system (Technegas?) uses?99mTc on an ultrafine dispersion of carbon. This results in particle diameters of 5-140 nm.????

- Examples of this type of procedure include?99mTc diethylenetriamine penta-acetate (DTPA) lung ventilation studies, typically combined with?a perfusion study for the diagnosis of pulmonary embolism.

2. Inert gases :

- Inert gases can be inhaled by the patient and pass into the pulmonary venous circulation from the lungs. These gases can exchange freely between the blood and tissues. ????

- Examples of this type of procedure include Xenon-133 and Krypton-81m lung ventilation studies, typically combined with a perfusion study for the diagnosis of pulmonary embolism.

Oral

• Two examples of radionuclide imaging studies where the radiopharmaceutical is administered orally are :

1. Thyroid imaging, where iodine-123 (123I) is given in the form of sodium iodide solution.

2. Gastric emptying in either liquid or solid phase. For liquid phase gastric emptying, a solution of indium-111 (111In) chloride is used, and for solid phase gastric emptying,?99mTc colloid - mixed typically with scrambled egg - is used.

Other examples

• Technetium-99m pertechnetate administered via a bladder catheter for direct radionuclide cystography.
• Subcutaneous injection of?99mTc colloid for lymphoscintigraphy. For outlining lymphonodular reticulocyte function, injection is into the web spaces between the fingers or toes. For identification of the first draining node from a breast tumor (the sentinel node), the radiopharmaceutical is injected subcutaneously around the nipple.
• Technetium-99m pertechnetate eye drops in normal saline used for assessment of lacrimal drainage.

Mechanisms of Localization of Radiopharmaceuticals :-

• Consider the topic of the mechanisms by which radiopharmaceuticals are localized within the patient under these headings :-

Transport mechanisms

1. Simple Diffusion

- Following dilution in a body compartment such as plasma, a simple diffusion process along a concentration gradient takes place allowing the substance to cross a permeability barrier, such as?99mTc pertechnetate as a brain scanning agent.

2. Facilitated diffusion

- Factors such as lipophilicity favor passive transport through a lipid membrane. An example is brain uptake of?99mTc hexamethylpropyleneamine (HMPAO) - more commonly known as exametazime - through the blood/brain barrier.

- Fig 1?shows a?99mTc DPTA brain image and?Fig 2?shows a transaxially single-photon emission computed tomography (SPECT)?99mTc HMPAO brain image

3. Active transport mechanisms

- Energy is consumed during the transport process, such as during uptake of Thallium-201 (201Tl ) by the myocardium.?The?201Tl thallous ions are taken up by the active transport system for potassium.

- An example of an active transport mechanism is where?201Tl is used for myocardial perfusion studies (Fig 3).

Immunological mechanisms

• Monoclonal antibodies have the capacity to recognise and interact with single antigens and potentially identify and target specific groups of cells such as blood cells and tumours. Unfortunately significant levels of activity may be taken up by tissues other than the target, leading to poor specificity and the technique has not found widespread clinical application.
• An example is an antigen-binding fragment (Fab) of anti-carcinoembryonic antigen (anti-CEA) antibody labelled with?99mTc used for imaging colorectal cancer (Fig 4).

Capillary trapping

• Intravenous injection of a particulate suspension with particles of diameter >10-15 μm (the diameter of pulmonary precapillaries) results in the trapping of particles in the pulmonary capillary bed (Fig 5).
• An example 99mTc MAA lung perfusion studies, typically combined with a ventilation study for the diagnosis of pulmonary embolism.

Receptor binding

• Receptor sites on molecules offer the possibility for highly specific radiotracers. For example,?111In-labelled pentetreotide, an analogue of the neuropeptide somatostatin, can be used to image tumors with somatostatin receptors, such as carcinoids, pancreatic endocrine tumors, neuroblastomas and paragangliomas (Fig 6).

Physiochemical adsorption

• Methylene diphosphonate (MDP) localization occurs primarily by adsorption into the mineral phase of the bone (Fig 7).
• Methylene diphosphonate concentrations are significantly higher in amorphous calcium than in mature hydroxyapatite crystalline structures, which helps to explain its concentration in areas of increased osteogenic activity.

Phagocytosis

• Uptake of radiopharmaceuticals by phagocytosis occurs when particles of 3 nm to 10 mm diameter are engulfed by phagocytic cells such as the Kupffer cells of the liver or the macrophages of the spleen and bone marrow. This is brought about by recognition of the particle by receptors on the cell surface.
• The use of?99mTc-tin and Sulphur colloids for liver scanning are examples of this (Fig 8).

Metabolic incorporation

• Radioisotopes of specific elements follow identical metabolic pathways to non-radioactive isotopes.- An example of this is the use of?123I for thyroid imaging (Fig 9). Radioactive iodine follows identical metabolic pathways to the natural, non-radioactive isotopes.
• The positron-emitting nuclide?18F in the chemical form of FDG is a glucose analogue; its increased uptake correlates with increased glucose metabolism.
• This has imaging applications in oncology, neurology and cardiology.

Chemotaxis

• Chemotaxis describes the movement of a cell such as a leukocyte in response to a chemical stimulus.
• For example,?111In-labelled leucocytes respond to products formed in immunologic reactions by migrating and accumulating at the site of the reaction as part of an overall inflammatory response.

Cell sequestration

• Red blood cells are withdrawn from the patient, labelled with?99mTc and slightly damaged by heating in a water bath for approximately 30 minutes. After they have been reinjected, the spleen's ability to recognize and remove (i.e. sequester) the damaged red blood cells is evaluated.
• This procedure allows for the evaluation of both splenic morphology and function.
• Fig 10?shows four views from a?99mTc damaged red cell splenic study.

Perfusion

• Relative perfusion of a tissue of organ system is an important diagnostic element in many nuclear medicine procedures.
• For example, the lung perfusion image is used in the diagnosis of pulmonary embolism.

Examples of Radiopharmaceutical and It's Mechanisms :-

Active Transport :

• involves the use of normal metabolic pathway in the body to transport the radiopharmaceutical across the cell membrane and into the cell.

Simple/exchange diffusion :

• the radiopharmaceutical diffuses across cells membranes and then binds/attaches to a cell component.

Specific receptor binding :

• the radiopharmaceutical binds to high-affinity receptor sites.

Specific binding to tumor antigens :

• specific binding of a radiolabelled antibody to surface antigens on tumour cells.

Miscellaneous mechanisms & and Increased tumor metabolism :