Targeting overexpressed tumor cell receptors with radiolabeled molecules: Biological targets, clinical applications, and translational challenges

Cancer remains a leading cause of mortality worldwide, and early diagnosis and effective targeted therapy are often constrained by the lack of tumor-specific biomarkers. Overexpressed cell-surface receptors provide accessible targets for precision molecular imaging and radionuclide therapy, enabling selective visualization and treatment of malignancies while minimizing off-target effects in normal tissues. This review synthesizes the current landscape of biomarker-targeted radiopharmaceuticals, highlighting clinically approved agents, emerging molecular scaffolds, and key criteria for optimal targeting and imaging performance. Clinically approved PSMA- and SSTR2-targeted radiotracers exemplify the success of this approach, enabling highly sensitive and specific detection of prostate cancer and neuroendocrine tumors, respectively. In contrast, many other radiolabeled molecules face substantial challenges in regulatory approval and clinical translation. Overall, exploitation of overexpressed tumor biomarkers for targeted imaging and therapy holds considerable promise for transforming oncology diagnostics and improving patient outcomes through precision molecular medicine.