Nuclear Medicine in Diagnosis and Therapy: Physical Principles, Clinical Applications, and the Role of Medical Physics in Quality Assurance and Radiation Safety

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Nuclear medicine is an advanced application of medical physics that uses radiopharmaceuticals to assess the physiological function of organs and tissues and to treat selected diseases, particularly certain malignancies. The field integrates nuclear physics, radiochemistry, biology, and clinical medicine by tracking the distribution of radioactive compounds within the body or directing them toward specific tissues. This article reviews the physical principles of radioactive decay and radiation interactions; imaging methods based on gamma cameras, single-photon emission computed tomography (SPECT), and positron emission tomography (PET); and the diagnostic and therapeutic applications of radiopharmaceuticals. It also discusses the role of the medical physicist in activity measurement, internal dosimetry, equipment calibration, quality control, and radiation protection. The article emphasizes that integrating physical measurements with clinical assessment is essential for obtaining reliable diagnostic information and delivering safe, appropriate radionuclide therapy. Nuclear medicine; medical physics; radiopharmaceuticals; PET; SPECT; internal dosimetry; radionuclide therapy; quality assurance; radiation protection. Nuclear medicine is a diagnostic and therapeutic medical specialty that uses measured quantities of radioactive materials attached to chemical or biological compounds known as radiopharmaceuticals. Following administration, these agents distribute according to their chemical and biological properties. The radiation they emit can be detected to produce images reflecting organ function or the activity of disease processes. Unlike many anatomical imaging modalities, nuclear medicine provides functional and molecular information that may reveal pathological changes before clear structural abnormalities become apparent. Nuclear medicine is not limited to diagnosis; it also includes radionuclide therapy, in which a radioactive agent is selected to deliver radiation to a specific tissue or biological target. The success of these procedures depends on selecting an appropriate radionuclide and carrier molecule, accurately measuring activity, understanding biodistribution and radioactive decay, and estimating absorbed dose in organs and tissues. These requirements establish medical physics as an essential discipline for equipment performance, measurement accuracy, and procedural safety . Physical Principles of Nuclear Medicine Nuclear medicine relies on radioactivity, the spontaneous transformation of an unstable atomic nucleus into a more stable state accompanied by the emission of particles or photons. Important emissions include gamma rays, beta-minus particles, positrons, and alpha particles. The emission type, radiation energy, and physical half-life determine the characteristics of a radionuclide and its diagnostic or therapeutic suitability. The number of radioactive nuclei decreases over time according to the radioactive decay law: N(t) = N₀ e^(−λt) where N(t) is the number of nuclei remaining at time t, N₀ is the initial number, and λ is the decay constant. The decay constant is related to the physical half-life (T½) by: T½ = ln(2) / λ Radioactive activity (A), which represents the number of nuclear transformations per unit time, is given by A = λN and is measured in becquerels (Bq), where one becquerel corresponds to one nuclear transformation per second. Physical half-life should be distinguished from biological half-life. The former describes nuclear decay, whereas the latter describes biological removal of the substance from the body. Together, they determine the effective half-life, which approximately describes how long activity remains in the body. Radiopharmaceuticals and Radionuclide Selection A radiopharmaceutical generally consists of a radionuclide attached to a carrier molecule or compound that targets a particular organ, receptor, or metabolic pathway. Radionuclide selection depends on nuclear properties such as emission type, photon energy, and half-life, while the carrier largely determines biological distribution and target binding. Examples of diagnostic radionuclides include technetium-99m (⁹⁹ᵐTc), which has properties suitable for gamma-camera imaging, and fluorine-18 (¹⁸F), which is used in many PET examinations. One example is ¹⁸F-FDG, which provides information about relative glucose utilization in different tissues. Therapeutic applications include iodine-131 (¹³¹I), lutetium-177 (¹⁷⁷Lu), and radium-223 (²²³Ra) for selected clinical indications. Radiopharmaceutical selection also requires consideration of chemical and radiochemical purity, stability, activity at the time of administration, and pharmacokinetic behaviour. Preparation and quality testing must comply with applicable professional and regulatory requirements. Nuclear Medicine Imaging Techniques Gamma Camera and Scintigraphy A gamma camera detects gamma photons emitted by the radiopharmaceutical within the patient. The system typically includes a collimator that selects the directions of accepted photons, a scintillation crystal that converts photon energy into light, and photomultiplier tubes or electronic detectors that convert the signal into data. Planar images are used to assess radiopharmaceutical distribution in organs. Single-Photon Emission Computed Tomography (SPECT) SPECT acquires projection images from multiple angles using a rotating gamma camera. These projections are then reconstructed computationally into three-dimensional sections representing activity distribution within the body. Detector resolution, patient motion, attenuation, scatter, data corrections, and reconstruction algorithms influence image quality and quantitative accuracy. Combining SPECT with CT provides both functional and anatomical information and requires accurate image registration and attenuation correction. Positron Emission Tomography (PET) PET uses positron-emitting radionuclides. After emission and partial loss of kinetic energy, a positron annihilates with an electron, usually producing two photons, each with an energy of 511 keV, travelling in nearly opposite directions. The scanner detects the two photons in coincidence within a defined time window. Coincidence events define lines of response that are used to reconstruct activity distribution. PET is commonly combined with CT or MRI to localize lesions anatomically and improve interpretation. PET and SPECT image quality depends on system sensitivity, spatial and temporal resolution, detector efficiency, physical corrections, administered activity, acquisition timing, and patient motion. Quantitative assessment therefore requires appropriate calibration and system-performance verification . Clinical Applications of Nuclear Medicine Nuclear medicine has a wide range of diagnostic applications depending on the organ and physiological function being evaluated. In cardiology, myocardial perfusion imaging can assess blood flow and cardiac function. In endocrinology, radioiodine studies are used to evaluate thyroid function and selected thyroid disorders. Bone scans can detect changes in bone activity, while renal studies assess renal function and drainage. PET examinations are used in the evaluation of many cancers, treatment response, and selected neurological and inflammatory disorders. Radionuclide therapy delivers ionizing radiation to a target tissue using a radiopharmaceutical. Examples include ¹³¹I treatment for selected thyroid disorders, ¹⁷⁷Lu-labelled compounds that target specific receptors or antigens, and ²²³Ra for selected cases of bone metastases. The indication and balance of benefits and risks must be assessed by the responsible clinical team for each patient. Internal Dosimetry and the Role of the Medical Physicist Internal dosimetry is a major area of medical physics in nuclear medicine. It aims to estimate the energy deposited by radiation in a patient's organs and tissues following administration of a radiopharmaceutical. This requires measuring activity, determining its spatial and temporal distribution, and calculating absorbed dose while accounting for radiation type, energy, and tissue characteristics. Absorbed dose can be expressed in simplified form as: D = Eabs / m where D is absorbed dose, Eabs is absorbed energy, and m is tissue mass. Absorbed dose is measured in gray (Gy), equivalent to joules per kilogram. More advanced clinical applications may use models such as the MIRD schema, voxel-based calculations, and Monte Carlo simulations when appropriate data and resources are available. Medical physicists contribute by calibrating activity meters (dose calibrators), verifying activity measurements before administration, calibrating quantitative imaging systems, performing phantom studies, evaluating attenuation and scatter correction, and analysing uncertainty in dose calculations. In radionuclide therapy, serial measurements after administration can help estimate radiopharmaceutical kinetics and time-integrated activity, supporting absorbed-dose estimates for target and normal organs. Recent guidance emphasizes documenting measurement and calculation methods and uncertainty sources, while supporting the development of more patient-specific dosimetry . Quality Assurance and Radiation Protection Quality assurance in nuclear medicine aims to ensure that equipment, radiopharmaceuticals, and procedures provide reliable and reproducible performance. Quality-control tests include detector uniformity, spatial resolution, sensitivity, energy resolution, count-rate performance, and the operation of processing and reconstruction systems. SPECT, SPECT/CT, and PET/CT systems require periodic testing with suitable sources and phantoms, with results documented and compared against baseline values and acceptance limits. Activity meters must also be tested to verify their response to different radionuclides. Radiation protection aims to minimize unnecessary exposure to staff, patients, and the public. It includes appropriate shielding, controlled work areas, monitoring of surface or airborne contamination when relevant, and safe management of radioactive waste. The principles of justification and optimization should be applied, while time, distance, and shielding are used to reduce occupational exposure. Therapeutic procedures may also require clear instructions for patients and caregivers regarding post-treatment precautions, according to the radionuclide, administered activity, and local regulations. Medical physicists contribute to quality and protection protocols, staff training, incident investigation, and review of recorded activities and doses. These tasks should be performed within a multidisciplinary team and in accordance with applicable standards and regulations . Nuclear medicine faces technical and scientific challenges, including limited spatial resolution compared with some anatomical imaging modalities, attenuation and scatter effects, motion, difficulties in quantitative measurements at low count levels, and individual variability in radiopharmaceutical biodistribution. In radionuclide therapy, additional uncertainties arise in absorbed-dose estimation and biological response, together with the need for standardized and reproducible protocols. Future directions include more sensitive and higher-resolution detectors, improved quantitative imaging, integration of anatomical, functional, and molecular information, and the use of artificial intelligence for image reconstruction, organ segmentation, and data analysis. Theranostics combines a diagnostic radiopharmaceutical that identifies a biological target with a therapeutic agent directed toward the same target. Patient-specific dosimetry may help optimize treatment, but its implementation requires standardized measurement and calculation methods, clinical validation, and transparent uncertainty reporting . Nuclear medicine is an advanced field integrating nuclear physics, medical imaging, biological sciences, and clinical applications. It provides important tools for functional diagnosis and targeted therapy. Medical physics contributes by ensuring accurate activity and dose measurements, improving quantitative image quality, calibrating equipment, and implementing quality assurance and radiation protection programmes. The expansion of radionuclide therapy and theranostics increases the need for internal dosimetry and treatment personalization according to individual patient characteristics. Accordingly, the inclusion of a qualified medical physicist in the nuclear medicine team is essential for reliable results and the safety of patients and staff.