Targeted Radionuclide Therapy: A Systematic Review of Advances, Challenges, and Future Directions

Abstract

Targeted radionuclide therapy (TRT) has emerged as a promising approach for treating malignancies by delivering ionizing radiation directly to tumor cells while sparing healthy tissues, thereby addressing a critical need in precision oncology. This systematic review synthesizes the current state of TRT, focusing on its principles, clinical applications, and evolving challenges, with the aim of identifying gaps and opportunities for future research. We conducted a comprehensive analysis of peer-reviewed literature to evaluate advancements in radiopharmaceutical design, cancer-specific targeting strategies, and the integration of TRT with other therapeutic modalities, including theranostics. The findings highlight significant progress in treating hematologic and solid tumors, particularly prostate cancer and neuroendocrine neoplasms, yet underscore persistent hurdles such as dosimetric optimization, radionuclide availability, and long-term toxicity management. Dosimetry remains a critical factor in balancing efficacy and safety, while supply chain limitations for therapeutic isotopes pose practical barriers to widespread adoption. Emerging trends, such as novel radionuclides and combination therapies, suggest a transformative potential for TRT, though further preclinical and clinical validation is needed. This review concludes that while TRT has demonstrated substantial clinical benefits, its full potential hinges on addressing logistical, technical, and biological challenges through interdisciplinary collaboration and innovation. The insights presented here provide a foundation for future research directions and clinical translation in this rapidly evolving