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Novel Radionuclide Applications: The characteristic of ¹⁶¹Tb to simultaneously emit β particles and Auger electrons can more effectively kill heterogeneous tumors.
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Conclusion: Establishing a New Paradigm for Precision Diagnosis and Treatment
The development of PSMA-targeted diagnostic and therapeutic technologies marks the entry of prostate cancer into a new era of "theranostics." From elucidating molecular mechanisms to clinical practice, PSMA has evolved from a simple biomarker to a core target in multimodal diagnostic and therapeutic systems. PSMA PET/CT, with its high sensitivity and specificity, has significantly improved the accuracy of prostate cancer diagnosis, particularly in detecting small metastatic lesions. It has become the preferred imaging modality for staging intermediate- and high-risk prostate cancer, localizing biochemical recurrence, guiding treatment decisions, and providing a foundation for precision therapy in advanced patients.
In the therapeutic domain, radioligand therapies such as [¹⁷⁷Lu]Lu-PSMA-617 and ¹⁶¹Tb-PSMA-I&T have offered optimized survival benefits and quality of life improvements for mCRPC patients. Novel therapeutic strategies, including PSMA-directed PROTACs and bispecific antibodies, show potential for overcoming resistance.
Future refinement of the PSMA diagnostic and therapeutic system will focus on three directions: (1) precise patient selection, optimizing treatment populations based on multi-omics biomarkers (such as PSMA expression levels, AR variant status, DNA repair defects, etc.); (2) standardization of diagnostic and therapeutic workflows, establishing standardized operating procedures according to the 2025 Chinese Expert Consensus; and (3) integration of innovative technologies, including AI-assisted PSMA PET image analysis, personalized dose optimization algorithms, and the development of new radionuclides/ligands. As key clinical trials advance, precision intervention strategies tailored to different disease stages will be further refined, ultimately achieving the dual goals of extending survival and improving quality of life.
In summary, the development of the PSMA-targeted diagnostic and therapeutic system not only reshapes clinical practice in prostate cancer but also ushers in a new era of precision nuclear medicine for treating solid tumors. Research in this field, both basic and translational, provides a paradigm that can be emulated for targeted diagnostics and therapeutics in other solid tumors. However, issues such as the cost, accessibility, and resistance of PSMA-targeted diagnostics and therapies remain to be addressed. Future efforts will focus on optimizing technology, expanding indications, and exploring new combination strategies (e.g., with novel endocrine therapies) to further improve patient outcomes.
