Integrating Positron Emission Tomography Combined with Computed Tomography Imaging into Advanced Radiation Therapy Planning: Clinical Applications, Innovations, and Challenges

Positron emission tomography combined with computed tomography (PET/CT) has revolutionized radiation oncology by merging functional and anatomical imaging to enhance tumor characterization, guide treatment precision, and support individualized patient care. This review critically evaluates the clinical applications of PET/CT-guided radiation therapy, highlighting its evolving impact, technical innovations, limitations, and future research directions. Key clinical uses – such as improved target delineation, adaptive therapy, and treatment response monitoring – are explored alongside the diagnostic performance of diverse radiotracers including 18F-fluorodeoxyglucose, prostate-specific membrane antigen-targeted agents, and hypoxia-specific probes. We examine advanced methodologies such as deformable image registration, radiomics, and artificial intelligence (AI)-driven segmentation for their potential to reduce interobserver variability and streamline radiotherapy (RT) workflows. The review also addresses persistent barriers, including limited tracer specificity, spatial resolution constraints, integration complexity, and high implementation costs. Beyond technical discussions, we reflect on emerging ethical considerations, such as transparency in AI-driven planning, patient consent in algorithm-assisted treatment decisions, and the need for equitable access to PET/CT technologies. We emphasize the importance of interdisciplinary collaboration and standardized imaging protocols to optimize clinical adoption. With continuous innovation and global access initiatives, PET/CT-guided RT is poised to play a leading role in shaping the future of precision oncology.