Positron Emission Tomography (PET) Physics: Fundamentals, Detectors, and Future Applications<br />by Lecturer Dhurgham Yousif Jawad<br /><br />Abstract<br /><br />This article reviews the principles of Positron Emission Tomography (PET) physics, types of detectors and modern measurement techniques (including TOF, SiPM, and digital PET), image processing and quantitative correction components, and the most important current and future applications such as PET/CT and PET/MRI, total-body PET, and advances in radiopharmaceuticals and theranostics. The discussion is based on reviews, research, and clinical practices from reputable journals and projects (PMC).<br /><br />1. Physical Principles of PET<br /><br />1.1 Positron Emission and Annihilation Events<br />In theory, a radioactive nucleus emits a positron through β⁺ decay. After a short path (depending on the positron’s energy and tissue density), the positron encounters a local electron, resulting in an annihilation that produces two photons of 511 keV each, emitted nearly in opposite directions (180°). Detecting both photons simultaneously (coincidence) allows activity localization along the Line Of Response (LOR). This is the core principle of PET measurement.<br /><br />1.2 Spatial Resolution and Sensitivity Constraints<br />Spatial resolution is affected by several factors: positron range before annihilation, non-collinearity caused by momentum, scintillator pixel size, and Depth-Of-Interaction (DOI) resolution. Sensitivity depends on detector ring design, axial coverage, and device attenuation factors.<br /><br />2. Components of PET Systems: Detectors and Sensors<br /><br />2.1 Scintillators<br />Modern PET systems employ crystals such as LSO/LYSO, which provide high density, short decay time, and high light yield. These offer superior TOF performance and sensitivity compared to older crystals like BGO.<br /><br />2.2 Light Detectors: From PMTs to SiPMs<br />Traditional photomultiplier tubes (PMTs) have largely been replaced over the last two decades by silicon photomultipliers (SiPMs). SiPMs are compact, MRI-compatible, offer higher photon sensitivity, and enable better timing—paving the way for digital PET.<br /><br />2.3 Depth-of-Interaction (DOI)<br />DOI techniques, such as multi-layered scintillators and advanced light readout methods, reduce parallax errors and improve spatial resolution at the edges of the field of view.<br /><br />3. Time-of-Flight (TOF) Techniques and Clinical Impact<br /><br />TOF measures the slight difference in arrival times between the two photons to reduce uncertainty along the LOR, improving the signal-to-noise ratio (SNR). Advances in crystals and SiPMs have made TOF standard in modern PET scanners, especially beneficial in large patients or low-dose studies.<br /><br />4. Image Processing and Quantitative Corrections<br /><br />4.1 Required Corrections<br /><br />Attenuation Correction: Compensates for photon absorption in tissue. PET/CT uses CT-derived maps, while PET/MR relies on MR-based AC methods or AI due to MR’s limitations.<br /><br />Scatter, randoms, sensitivity, and normalization corrections.<br /><br />Reconstruction: Algorithms such as OSEM with Point Spread Function (PSF) modeling and TOF integration enhance both image quality and quantification.<br /><br />4.2 Quantitative Measures<br />Standardized Uptake Value (SUV) is widely used clinically. For precise quantification and dynamic studies, calibration, kinetic modeling, and accurate timing are required. Total-body PET enables whole-body dynamic imaging and advanced pharmacokinetic studies.<br /><br />5. Radiotracers and Radiopharmaceutical Advances<br /><br />While [¹⁸F]FDG remains the most common tracer, newer agents have expanded PET’s scope: PSMA for prostate cancer, DOTATATE for neuroendocrine tumors, amyloid tracers for neurology, and others. Emerging isotopes (⁶⁸Ga, ⁸⁹Zr, ¹⁸F, ⁶⁴Cu) allow molecular targeting and theranostics (combined diagnostics and therapy).<br /><br />6. Hybrid and Advanced Systems<br /><br />6.1 PET/CT and PET/MR<br /><br />PET/CT integrates attenuation correction and is the clinical standard in oncology.<br /><br />PET/MR offers superior soft-tissue contrast with lower radiation dose but requires specialized attenuation correction techniques.<br /><br />6.2 Total-Body PET<br />Scanners like uEXPLORER enable full-body imaging with dramatically increased sensitivity, allowing reduced doses, faster scans, and dynamic tracking of tracer distribution across organs—valuable in drug development, neurology, and oncology.<br /><br />7. Selected Clinical and Research Applications<br /><br />Oncology: Diagnosis, treatment planning, recurrence detection; tracers like PSMA and DOTATATE improved specificity.<br /><br />Neurology: Brain metabolism imaging, receptor mapping, amyloid imaging for Alzheimer’s.<br /><br />Infection/Inflammation: Specialized tracers for infectious diseases.<br /><br />Drug Development: Total-body PET enables powerful pharmacokinetic and biodistribution studies.<br /><br />8. Technical and Regulatory Challenges<br /><br />Attenuation correction in PET/MR (especially for bone and implants).<br /><br />High costs and infrastructure demands for total-body PET and novel tracers.<br /><br />Need for calibration and multicenter harmonization for reliable quantitative studies.<br /><br />9. The Future of PET — Promising Directions<br /><br />Expansion of total-body PET for dynamic whole-body studies.<br /><br />Improved sensitivity and timing via faster crystals, advanced SiPMs, and sub-100 ps TOF.<br /><br />Digital PET for direct photon-to-digital conversion.<br /><br />Artificial Intelligence and Deep Learning for reconstruction, MR-based attenuation correction, and dose reduction.<br /><br />Theranostics, linking diagnostic tracers with therapeutic isotopes for personalized medicine.<br /><br />10. Conclusion<br /><br />PET physics bridges nuclear principles with cutting-edge detector technology, advanced timing (TOF), and complex quantitative processing to deliver high-quality, comparable images. Ongoing innovations—particularly total-body imaging, digital PET, and AI—are expanding PET’s role in early disease detection, drug research, and theranostics. Overcoming logistical and standardization challenges will require collaboration among physicists, clinicians, industry, and regulatory bodies.<br /><br />University of Al-Mustaqbal — The First University in Iraq