Theranostics in nuclear medicine: the era of precision oncology.

Abstract

Theranostics represents a transformative advancement in nuclear medicine by integrating molecular imaging and targeted radionuclide therapy within the paradigm of personalized oncology. This review elucidates the historical evolution and contemporary clinical applications of theranostics, emphasizing its pivotal role in precision cancer management. The theranostic approach involves the coupling of diagnostic and therapeutic radionuclides that target identical molecular biomarkers, enabling simultaneous visualization and treatment of malignancies such as neuroendocrine tumors (NETs), prostate cancer, and differentiated thyroid carcinoma. Key theranostic radiopharmaceutical pairs, including Gallium-68-labeled DOTA-Tyr3-octreotate (Ga-68-DOTATATE) with Lutetium-177-labeled DOTA-Tyr3-octreotate (Lu-177-DOTATATE), and Gallium-68-labeled Prostate-Specific Membrane Antigen (Ga-68-PSMA) with Lutetium-177-labeled Prostate-Specific Membrane Antigen (Lu-177-PSMA), exemplify the "see-and-treat" principle central to this modality. This article further explores critical molecular targets such as somatostatin receptor subtype 2, prostate-specific membrane antigen, human epidermal growth factor receptor 2, CD20, and C-X-C chemokine receptor type 4, along with design principles for radiopharmaceuticals that optimize target specificity while minimizing off-target toxicity. Advances in imaging platforms, including positron emission tomography/computed tomography (PET/CT), single-photon emission computed tomography/CT (SPECT/CT), and hybrid positron emission tomography/magnetic resonance imaging (PET/MRI), have been instrumental in accurate dosimetry, therapeutic response assessment, and adaptive treatment planning. Integration of artificial intelligence (AI) and radiomics holds promise for enhanced image segmentation, predictive modeling, and individualized dosimetric planning. The review also addresses regulatory, manufacturing, and economic considerations, including guidelines from the United States Food and Drug Administration (USFDA) and European Medicines Agency (EMA), Good Manufacturing Practice (GMP) standards, and reimbursement frameworks, which collectively influence global adoption of theranostics. In summary, theranostics is poised to become a cornerstone of next-generation oncology, catalyzing a paradigm shift toward biologically driven, real-time personalized cancer care that seamlessly links diagnosis and therapy.