Colorectal Cancer: A Landscape of New Potential Radiopharmaceuticals

In recent years, advancements in imaging techniques have contributed to a gradual yet promising reduction in colorectal cancer-related mortality. Among these, positron emission tomography (PET), particularly in combination with computed tomography using 2-deoxy-2-[fluorine-18]fluoro-D-glucose ([¹⁸F]FDG), has emerged as a valuable non-invasive diagnostic tool. However, the application of [¹⁸F]FDG-PET in colorectal cancer remains limited because of the radiotracer's pharmacokinetics and metabolic characteristics. As a result, [¹⁸F]FDG-PET is not routinely recommended for the initial diagnosis or staging of colorectal cancer but is primarily used for assessing treatment response and disease surveillance. Additionally, colorectal cancer imaging with [¹⁸F]FDG presents challenges related to false-positive results caused by radiotracer uptake in non-malignant conditions such as inflammatory bowel disease, polyps, Crohn's disease, and colitis. This inability to reliably distinguish between benign and malignant lesions remains a significant limitation in colorectal cancer imaging. To overcome these challenges, ongoing research is focused on the development of novel radiotracers capable of improving the specificity and accuracy of PET imaging in colorectal cancer. New radiolabeled probes are being investigated, including natural molecules, inflammatory markers, and target-specific immune elements, labeled with [¹⁸F], [⁶⁸Ga], [¹¹C], and [⁶⁴Cu], which have shown potential in preclinical studies. Among emerging radiopharmaceuticals for colorectal cancer, only [⁶⁸Ga]Ga-HNI01 and [⁶⁸Ga]Ga-FAPI-04 have advanced to preliminary clinical evaluation phases. Despite promising initial diagnostic performance, these investigations remain limited in scale and scope, necessitating further rigorous, large-scale clinical trials to validate efficacy and safety. All these advancements could significantly enhance colorectal cancer detection and characterization, leading to earlier diagnoses and better patient outcomes.