Molecular guidance for planning external beam radiation therapy in oncology

The origin of radiotherapy dates back to 1895-immediately after the discovery of X-rays. Since the beginning, efforts were focused on developing ways to improve the accuracy of radiation delivery. Molecular imaging allows the visualization of surrogates of several pathophysiological characteristics of tumor tissue (e.g., proliferation, metabolism, hypoxia, perfusion), allowing tailoring of dose distribution based on the tissue's features and biological patterns within the tumor. A significant improvement in the ability of modern radiotherapy to precisely target tumor while avoiding irradiating normal tissues can be achieved by integrating molecular imaging into an individualized radiation treatment planning. PET data are the most common molecular images used for tumor volume delineation and assessment of pathophysiological characteristics of tissue. The type of radiopharmaceutical used allows visualization and understanding of different pathophysiologic information. The most commonly used among all PET tracers is the 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG). [18F]FDG is currently the mainstay of PET use in radiotherapy. With the aim of identifying specific biological tumor processes and offering valuable information that can assist radiation oncologist to modulate radiotherapy's doses and volumes, several other molecular imaging tracers emerged in the last few years. Non-[18F]FDG tracers commonly used in radiation oncology include [11C]Methionine ([11C]MET) for brain tumors; [18F]FDOPA for brain and neuroendocrine tumors; radiolabeled somatostatin analogs for somatostatin-receptor positive tumors; 3'-deoxy-3'-[18F]fluorothymidine ([18F]FLT) and 18F-fluoromisonidazole (18F-FMISO) to identify regions of radiation resistance within the tumor; and [11C]/[18F]Choline, [18F]/68Ga-PSMA, and 18F-Fluciclovine for prostate cancer.