NUCLEAR MEDICINE

                                        NUCLEAR MEDICINE

Content

1. Radionuclides
2. Radiopharmaceuticals
3. Planar Imaging
4. Planar Imaging
5. Quality Control
6. Image Quality

I. Radionuclides

Radionuclides, or radioactive isotopes, are essential tools in nuclear medicine procedures. The most commonly used medical radionuclides are technetium-99m (^99mTc), iodine-131 (¹³¹I), and fluorine-18 (¹8F). These radionuclides emit gamma rays that can be detected by gamma cameras and positrons that can be detected by PET scanners, allowing physicians to image their distribution in the body.

Technetium-99m is the workhorse radionuclide of nuclear medicine due to its ideal nuclear properties. It has a half-life of 6 hours, allowing for imaging to take place hours after injection without requiring the patient to remain in the clinic. It emits a 140 keV gamma ray that is well-suited for gamma camera detection. Over 80% of nuclear medicine procedures utilize ^99mTc-labeled radiopharmaceuticals. Some common ^99mTc radiotracers include ^99mTc-MDP for bone scans, ^99mTc-DTPA for renal function assessment, and ^99mTc-sestamibi for myocardial perfusion imaging.

Iodine-131 has a longer half-life of 8 days, making it useful for therapy in the treatment of thyroid cancer and non-cancerous thyroid conditions like Graves' disease. Its beta and gamma emissions allow both internal radiation treatment of thyroid tissue as well as external imaging to monitor treatment response and residual disease.

Fluorine-18 has a very short half-life of only 110 minutes, necessitating on-site production in a cyclotron and rapid administration to patients. However, its positron emissions make it ideal for PET imaging with radiotracers like ¹⁸F-FDG. ¹⁸F-FDG PET/CT has revolutionized oncology by providing high-resolution metabolic imaging, allowing earlier cancer detection and more accurate staging, restaging, and treatment response assessment compared to anatomical imaging alone.

In summary, the choice of radionuclide depends on its nuclear properties like half-life, type of emission, and energy, and how these properties can be utilized for diagnostic imaging or targeted radiotherapy. The most important medical radionuclides are ^99mTc, ¹³¹I, and ¹⁸F, which form the basis for the vast majority of nuclear medicine procedures performed today.

II. Radiopharmaceuticals

Radiopharmaceuticals are the combination of a radionuclide with other components that allow for its targeting to specific organs, tissues, or biochemical processes in the body. These targeting components are called ligands and include small molecules, peptides, antibodies, and other targeting vectors. Radiopharmaceutical development requires extensive research to design new ligands that can be labelled with radionuclides and demonstrate specific uptake in the target of interest.

Some key considerations in radiopharmaceutical design include the following:

1. Choice of radionuclide based on desired application (imaging vs. therapy), half-life, and emissions as discussed above. Commonly used radionuclides are ^99mTc, ¹³¹I, and ¹⁸F.
2. Design of a ligand or targeting molecule that can selectively bind to or be taken up by the target tissue or biochemical process. Examples include small molecules like MDP that bind to hydroxyapatite in bone, peptides that bind to receptors overexpressed on cancer cells, and antibodies that bind to cell surface antigens.
3. Radiolabelling chemistry to attach the radionuclide stably to the ligand without altering its targeting properties. For example, ^99mTc can be attached to ligands using a technetium-carbonyl core, while 18F is attached to ligands using click chemistry. 
4. In vitro and in vivo validation in cell and animal models to demonstrate target specificity and favourable pharmacokinetics for imaging. Factors like uptake, clearance, metabolism, and dosimetry are evaluated.
5.  Regulatory approval through pre-clinical and clinical trials demonstrating safety, efficacy, and appropriate radiation dosimetry in humans for diagnostic use. Additional therapy trials are required for therapeutic radiopharmaceuticals.
6. Some of the most widely used radiopharmaceuticals include ^99mTc-MDP, ^99mTc-sestamibi, ¹⁸F-FDG, ¹³¹I-NaI, and many others. Continued research is developing new radiopharmaceuticals for emerging applications in personalized medicine and molecular imaging. Radiopharmaceutical design lies at the core of nuclear medicine.

III. Planar Imaging

Planar scintigraphy, also known as planar imaging, is a basic nuclear medicine procedure where gamma-emitting radiotracers are injected or administered to the patient and their biodistribution is imaged in two dimensions over time. Planar imaging is performed using a gamma camera, which is comprised of a large sodium iodide crystal scintillator coupled to an array of photomultiplier tubes.

When gamma photons emitted by the radiotracer interact with the crystal, light flashes are produced. These flashes are converted to electrical signals by the photomultiplier tubes and processed by a computer to form two-dimensional images. Lead collimators are placed in front of the crystal to selectively detect gamma rays from only certain angles, forming a "view" of the radiotracer distribution in the patient from that perspective.

Multiple planar views can be acquired from different angles around the patient and combined to provide anatomical localization of radiotracer uptake. For example, anterior, posterior, and lateral views are common for bone scintigraphy. Planar imaging is also performed dynamically over time to evaluate radiotracer kinetics and clearance from organs. Computer programs can generate time-activity curves and calculate quantitative parameters like blood flow.

While planar imaging only images one two-dimensional plane at a time, it has remained a mainstay of nuclear medicine due to its widespread availability, low cost, and ability to evaluate radiotracer biodistribution over time. It is well-suited for applications like bone scintigraphy, renal imaging, and evaluation of superficial organs. However, it suffers from limitations in localizing uptake in three dimensions and differentiating overlying structures.

IV. Tomography

Tomography refers to imaging techniques that can reconstruct the radiotracer distribution inside the body in three dimensions, overcoming the limitations of planar imaging. The two main tomographic modalities used in nuclear medicine are single photon emission computed tomography (SPECT) and positron emission tomography (PET).

SPECT involves the use of a gamma camera to acquire multiple planar views of the patient from different angles as the camera rotates around them. Computer programs then apply reconstruction algorithms to convert the multiple two-dimensional images into cross-sectional tomographic slices, allowing for three-dimensional visualization and localization of radiotracer uptake. This provides better separation of overlying structures compared to planar imaging. SPECT is commonly used with ^99mTc radiotracers and gamma-emitting radiotracers like ²⁰¹Tl.

PET imaging detects pairs of gamma photons (no single photons like in SPECT) emitted indirectly by positron-emitting radiotracers like ¹⁸F-FDG. Coincidence detection circuits are able to determine the simultaneous detection of the two 511 keV photons moving in opposite directions, allowing localization of their point of origin along a line of response. Multiple lines of response are acquired from different angles and reconstructed to form transaxial tomographic images with even higher resolution than SPECT. PET also provides quantitative measurements of radiotracer uptake.

The combination of PET with CT in PET/CT scanners has revolutionized molecular imaging by allowing accurate anatomical localization and attenuation correction of PET images. Hybrid SPECT/CT is also increasingly used. Tomography provides important advantages over planar imaging by localizing uptake three-dimensionally and distinguishing between adjacent structures, with SPECT and PET each having their own strengths and roles.

V. Quality Control

Quality control (QC) is an essential part of ensuring high-quality images and accurate diagnoses in nuclear medicine. Regular performance testing of gamma cameras and PET/CT systems is required to verify that they are functioning as expected and meeting prescribed performance criteria. QC tests include daily, weekly, monthly and annual tests of different parameters.

Daily QC involves testing the uniformity and integrity of the gamma camera or PET detector crystals. It also evaluates the constancy of energy, spatial resolution, and linearity. Weekly QC further tests the constancy of sensitivity and uniformity over time. Monthly QC expands to assess the accuracy of reconstructed scales and may include phantom imaging.

Annual QC represents a more rigorous and comprehensive evaluation. For gamma cameras, this involves imaging hot and cold rod sources as well as line source and flood field uniformity phantoms to characterize the camera's resolution, linearity, spatial accuracy and uniformity over the field of view. For PET/CT, annual QC fully characterizes the PET, CT, and combined system performance along with quality assurance of the radiopharmacy and dose calibrators.

QC data is tracked longitudinally to monitor for any changes or degradation in performance. Action levels are defined so that repairs or replacements can be made if parameters drift outside acceptable ranges. Facilities must also undergo regular performance audits by accrediting bodies. Strict adherence to QC ensures each exam's diagnostic quality and that quantitative tests remain consistent and comparable over time.

VI. Image Quality

Several factors impact the quality, diagnostic value, and quantitative accuracy of nuclear medicine images. These include the administered radiotracer dose and volume, patient characteristics, acquisition parameters, and image processing techniques.

1. Higher patient weight requires a higher administered dose to achieve comparable counts. The dose should also be adjusted based on the organ or system being imaged.
2. Optimal timing of imaging is important. For example, bone imaging 2-4 hours post-injection when radiotracer has cleared from soft tissues but concentrated in bone.
3.  Longer acquisition times improve counts and therefore image quality, but require minimizing patient motion to avoid blurring.
4.  For SPECT, using a higher number of projections (angles) and thicker camera heads with more detector crystals enhances spatial resolution and image quality.
5. Iterative reconstruction techniques can improve resolution compared to filtered back projection but are also more prone to noise.
6. For PET, using time-of-flight data, point-spread function modelling, and other corrections during reconstruction enhances quantitative accuracy and resolution.
7. Attenuation and scatter correction are important for PET and SPECT to avoid quantification errors caused by photon attenuation in tissue.
8. Proper smoothing, filtering, and post-processing can reduce image noise while preserving needed detail and resolution depending on the clinical task.