The next evolution of theranostics: from target discovery to integrated precision medicine

Clinical trial number: not applicable.For more than two decades, innovation in theranostics has been driven by one central scientific question: which molecular target should be imaged and treated next? This quest for actionable molecular targets transformed nuclear medicine, leading to landmark advances such as peptide receptor radionuclide therapy (PRRT) for neuroendocrine tumors and prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) for metastatic castration-resistant prostate cancer. The NETTER-1 and VISION phase III trials, together with subsequent EANM/SNMMI guidelines, established theranostics as one of the most successful examples of precision oncology (1)(2)(3)(4).Today, however, the field may be approaching a different challenge. As the number of clinically actionable molecular targets continues to expand, discovering another target is no longer sufficient, by itself, to drive the next major advances in theranostics. Increasingly, clinical impact depends on how effectively existing and emerging targets can be integrated into a broader precision medicine strategy. This evolution is reflected across the theranostic pathway. Quantitative molecular imaging, patient stratification, individualized dosimetry, computational treatment planning, therapeutic optimization, longitudinal response assessment, and adaptive treatment strategies are becoming major determinants of patient benefit rather than complementary components of radionuclide therapy (5)(6)(7)(8)(9). Collectively, these developments share a common objective: maximizing the clinical value of molecular targets that have already been identified. This Opinion argues that theranostics is entering a new stage of development. Future breakthroughs will undoubtedly continue to emerge from novel biological targets, but the principal driver of innovation is progressively shifting from target discovery toward the integrated clinical exploitation of those targets. This transition-from target discovery to integrated precision medicine-forms the conceptual basis of this Opinion. As illustrated in Figure 1, we propose that theranostics is entering an Integration Era in which the clinical value of molecular targets increasingly depends on their incorporation into comprehensive precision medicine workflows rather than on target identification alone.The success of theranostics was built upon a deceptively simple concept: a single molecular target could serve as a common biological gateway for both diagnosis and therapy. By linking molecular imaging with targeted radionuclide therapy, this principle fundamentally redefined the role of nuclear medicine, transforming it from a predominantly diagnostic specialty into a discipline capable of guiding and delivering personalized treatment. The demonstration that one molecular target could support disease visualization, patient selection, and therapeutic intervention represented a conceptual breakthrough that distinguished theranostics from both conventional imaging and systemic therapies (1,2).These achievements naturally stimulated an intense search for additional theranostic targets.Fibroblast activation protein (FAP), CXCR4, gastrin-releasing peptide receptor (GRPR), B7-H3, integrins, and numerous other emerging biomarkers continue to broaden the theranostic landscape, creating new opportunities across oncology and beyond (10)(11)(12). This continued diversification remains a major driver of innovation and will undoubtedly expand the clinical applications of radiopharmaceutical sciences.Importantly, this expansion should not be interpreted as a competition to identify the next major theranostic breakthrough. Rather, each new molecular target broadens the theranostic paradigm by addressing distinct tumour biologies, disease processes, and clinical settings.At the same time, however, the success of this target-driven innovation has fundamentally changed the questions facing the field. As the number of actionable molecular targets continues to increase, discovering another target is no longer sufficient, by itself, to ensure meaningful clinical impact.Instead, the challenge is progressively shifting toward understanding how each target can be translated into the greatest possible patient benefit. The central scientific question is therefore evolving from "What can we target?" to "How can we best use the targets we already have?"The success of theranostics has not eliminated the need for new molecular targets; it has changed the factors that determine their clinical impact. While target discovery remains fundamental, it is no longer sufficient, by itself, to maximize patient benefit. Increasingly, innovation depends on how effectively molecular targets are translated into clinical practice and integrated into precision medicine workflows. This shift is evident across virtually every stage of the theranostic pathway. Quantitative molecular imaging is evolving beyond lesion detection towards treatment planning and response prediction.Personalized dosimetry is increasingly recognized as an essential component of radiopharmaceutical therapy and is progressively moving beyond fixed-activity approaches to account for the substantial variability in radiation dose delivered to individual patients. Similarly, advances in computational modelling, artificial intelligence, treatment sequencing, and combination strategies all pursue a common objective: extracting greater clinical value from existing molecular targets rather than simply expanding the catalogue of actionable biomarkers (5)(6)(7)(8).These developments highlight an important conceptual distinction. Identifying a biologically relevant target is only the first step towards successful theranostics. Clinical benefit increasingly depends on a much broader set of factors, including robust patient selection, quantitative imaging, optimized radionuclide delivery, individualized dosimetry, response assessment, and treatment adaptation