Theranostics has transformed the management of solid tumours, particularly neuroendocrine tumours (NETs), through highly targeted radioligand therapies. NETs frequently overexpress somatostatin receptors (SSTR), which makes them highly suitable for theranostic approaches using radiolabelled peptides such as ⁶⁸Ga-DOTATATE for imaging and ¹⁷⁷Lu-DOTATATE for therapy.

The pivotal NETTER-1 trial (Strosberg et al., NEJM 2017) demonstrated a significant improvement in progression-free survival using ¹⁷⁷Lu-DOTATATE in patients with midgut NETs, setting a benchmark for theranostic applications. Recent advancements also include the development of SSTR antagonists and alpha emitters such as ²²⁵Ac-DOTATATE, showing potential for patients resistant to beta emitters.

Beyond NETs, theranostics is increasingly being explored in other solid tumours, including prostate, breast, and lung cancers, by identifying novel tumour-specific targets.

Prostate cancer is one of the most advanced and well-documented areas in theranostics. PSMA-targeted imaging and therapy have revolutionized the diagnosis and treatment of advanced disease, offering new options for patients with castration-resistant or metastatic prostate cancer.

The pivotal VISION trial (Sartor et al., NEJM 2021) demonstrated that ¹⁷⁷Lu-PSMA-617 improves both overall survival and radiographic progression-free survival in patients with metastatic castration-resistant prostate cancer (mCRPC). In addition, ²²⁵Ac-PSMA therapies have attracted attention as promising second-line or combination treatments, particularly in cases resistant to beta emitters.

Research is also expanding into GRPR imaging, dual-targeting ligands, and novel combination therapies, broadening the theranostic toolbox. Meanwhile, ⁶⁸Ga-PSMA PET/CT has become a standard for detecting biochemical recurrence and staging, supported by trials such as CONDOR and OSPREY.

Theranostics depends on precise imaging, accurate dosimetry, and technological innovation — making medical physics and instrumentation essential for the safe and effective delivery of radiomolecular therapy. Recent advances in total-body PET/CT, AI-based image analysis, and alpha-particle dosimetry are transforming how targeted treatments are measured and applied.

The development of total-body PET/CT scanners (Cherry et al., 2018) has enabled dynamic whole-body imaging with ultra-low doses and improved sensitivity. At the same time, AI applications now support segmentation, quantification, and response assessment — from dosimetry planning to image-guided therapy.

Alpha-emitter dosimetry (e.g., Ac-225, At-211) poses new challenges in microdosimetry and radiobiological modeling, prompting fresh approaches in camera technology, reconstruction algorithms, and radiopharmaceutical kinetics. Other innovations include novel detector systems, CZT cameras, and methods for non-invasive theranostic dose estimation.

Antibody drug conjugates (ADCs) combine the targeting specificity of monoclonal antibodies with the cytotoxic potential of radionuclides, chemotherapeutic agents, or immune-stimulating payloads. In theranostics, this platform is rapidly advancing — moving beyond traditional β-emitters to include α-emitters, immune activation, and multimodal conjugates.

Examples include diagnostic tools such as ⁸⁹Zr-trastuzumab and therapeutic agents like ²²⁷Th-HER2-ADCs, under active investigation in HER2-positive breast cancer, gastric cancer, and PSMA-expressing prostate cancer.

Next-generation approaches focus on:

• Peptide–drug conjugates (PDCs) for improved tumour penetration
• DARPins and miniproteins as compact, high-affinity scaffolds
• Radiovaccination strategies, coupling immunomodulators with radiotherapy
• Bispecifics and combination constructs, targeting multiple antigens or mechanisms

This diversification enhances biodistribution, tumour uptake, and therapeutic index, positioning ADCs and related formats as a promising frontier in radiomolecular precision medicine.

Identifying and validating new molecular targets lies at the heart of theranostics. Paired with innovations in radiochemistry, these advances are expanding the field far beyond traditional ligands such as somatostatin analogs and PSMA to include FAP, integrins, GPC3, cathepsins, and many more.

At the same time, modular chemistry, click-labeling strategies, and multimeric constructs are enabling faster synthesis, higher specificity, and improved pharmacokinetics — all key factors for successful clinical translation.

Highlights include:

• Fibroblast Activation Protein (FAP): A promising target across multiple solid tumours. ⁶⁸Ga-FAPI tracers have shown excellent tumour-to-background ratios, and therapeutic compounds (¹⁷⁷Lu-FAPI, ²²⁵Ac-FAPI) are under investigation (Lindner et al., JNM 2018; Baum et al., 2021).
• Integrins (e.g., αvβ3): Involved in angiogenesis and metastasis; targeted with RGD-based radioligands.
• New synthetic strategies: Monomer–dimer designs, bifunctional chelators (DOTA, NOTA), and bioorthogonal ligation methods enabling efficient labeling under mild conditions.
• Emerging targets: Molecules such as GPC3, mesothelin, and cathepsin S are showing high potential in hepatocellular, pancreatic, and breast cancers.

Together, these developments are shaping the next generation of theranostic radiopharmaceuticals and expanding clinical applications.

Theranostics is rapidly moving beyond its traditional indications. With advances in tumour biology, genetic profiling, and precision targeting, the field is expanding into new areas such as glioblastoma, gynaecologic cancers, paediatric oncology, and rare malignancies. Integrating pharmacogenetics, radiogenomics, and novel radiopharmaceutical designs is opening the door to a new era of personalised medicine in nuclear oncology.

Scientific progress includes:

• Glioblastoma & Substance-P targeting: NK1 receptor-targeted radioligands such as ²¹³Bi-Substance P have been evaluated for local therapy of recurrent glioblastoma (Albert NL et al., 2020).
• Pharmacogenetics: Research is investigating how genetic polymorphisms in DNA repair and drug transport pathways (e.g., ABCB1, SLCO1B3, GSTP1) influence responses to radioligand therapy.
• Education & access concepts: New approaches to training, capacity building, and global equity in theranostics are becoming central to the field.

Emerging concepts include multi-targeted theranostics, immunoradiotherapeutic combinations, and the use of AI-driven genetic decision tools to support patient selection.

The tumour microenvironment (TME) plays a critical role in cancer progression, immune evasion, and therapy resistance. In theranostics, imaging and targeting components of the TME — such as fibroblasts, extracellular matrix, and inflammatory markers — is opening new frontiers for diagnosis and patient stratification. TME-based diagnostics aim to go beyond morphology by visualising the functional and immunologic landscape of tumours.

Scientific advances include:

• FAPI (Fibroblast Activation Protein Inhibitors): ⁶⁸Ga-FAPI PET shows high uptake in a wide range of cancers with excellent tumour-to-background ratios, including malignancies with low FDG sensitivity (Giesel FL et al., JNM 2019).

• Next-generation ligands: Work is progressing on dimeric FAP constructs, halogenated analogues (e.g., ¹⁸F, ²¹¹At), and comparative imaging with FDG.

• Expanding toolkits: Novel pharmacophores, enzyme-activated probes, and strategies targeting matrix remodelling enzymes (e.g., MMPs, cathepsins).

TME diagnostics are increasingly essential for therapy selection, immunotherapy monitoring, and understanding tumour heterogeneity.

The tumour microenvironment (TME) is not only a diagnostic target — it is increasingly a therapeutic battlefield. Cancer-associated fibroblasts (CAFs), immune suppression zones, and stromal barriers all contribute to therapy resistance. TME-targeted radioligand therapy (RLT) is emerging as a powerful strategy to modulate or directly disrupt this environment. Incorporating FAP-targeted therapies, combination protocols, and multi-target constructs opens new possibilities for tumours previously unresponsive to conventional treatments.

Scientific advances include:

• FAP-targeted RLT: Agents such as ¹⁷⁷Lu-FAPI-46, ²²⁵Ac-FAPI, or dimeric ligands have shown promising early-phase results in various solid tumours (Ballal S et al., EJNMMI 2021; Baum RP et al., 2022).
• Combination therapies: Trials are exploring synergies with checkpoint inhibitors (e.g., anti-PD-L1) or anti-angiogenic agents (VEGF) to enhance efficacy and immune accessibility.
• Broader indications: FAP-targeted therapy is under investigation in gynaecologic cancers, GI tumours, and head and neck cancers through small cohorts and expanded access programmes.

Ongoing clinical studies are focusing on dosimetry, toxicity, and synergistic regimens — aiming to transform resistant “cold” tumours into immunologically “hot” tumours.

Sustainable, scalable, and innovative radioisotope production is a critical backbone of theranostics. The rising global demand for theranostic radiometals such as ¹⁷⁷Lu, ⁶⁸Ga, ²²⁵Ac, ¹⁶¹Tb, ²¹²Pb, and ²¹¹At makes production, processing, and regulatory readiness more important than ever. Emerging accelerator-based, generator-based, and reactor-independent production routes are reshaping how personalised radiopharmaceuticals can be delivered worldwide.

Scientific highlights include:

• ¹⁷⁷Lu and ²²⁵Ac: Among the most requested therapeutic isotopes, though supply remains limited. Cyclotron- and linac-based methods are being developed to meet growing clinical needs (Cutler C et al., SNMMI 2023).

• ¹⁶¹Tb: With its low-energy beta and Auger emissions, it offers enhanced cytotoxicity and is advancing through preclinical and early clinical phases (Müller C et al., PSI; Bergmann R et al., Helmholtz).

• Generator innovations: Systems such as ¹⁶⁶Dy/¹⁶⁶Ho, ²¹²Pb, and long-lived parent–daughter pairs are enabling decentralised isotope access.

• Chemistry and quality: Advances in chelator and separation chemistry, target recycling, and radiopurity control are supporting GMP compliance and regulatory approval.

TWC2026 provides a platform for producers, radiochemists, and regulators to exchange knowledge, present new technologies, and foster collaborations in this critical area of theranostics.

The future of theranostics relies on strong fundamental science. From radiobiological mechanisms to preclinical theranostic models and first-in-human studies, basic and translational research provides the foundation for innovation in radiomolecular precision medicine. Understanding DNA damage response, tumour microdosimetry, and cellular radiosensitivity is crucial to optimise the efficacy and minimise the toxicity of targeted radionuclide therapies.

Scientific advances include:

• Radiobiology of theranostics: Growing focus on alpha emitters such as ²²⁵Ac and ²¹¹At, as well as Auger emitters, which induce high-LET, localised DNA damage with unique repair dynamics (Pouget JP et al., 2021).
• Preclinical models: Humanised mouse strains, 3D tumour spheroids, and imaging-integrated biodistribution studies are accelerating translational research.
• Molecular targets: Molecules like GPC3, PSMA, and integrins are being evaluated alongside imaging and therapy agents, while biodosimetry, cell-cycle profiling, and genomic instability markers are under investigation as predictive tools.

The line between “basic” and “translational” research is increasingly blurred, as novel agents move rapidly from laboratory discovery to clinical proof-of-concept.

Combining targeted radionuclide therapy (TRT) with other treatment modalities is redefining precision oncology. Synergistic strategies involving immunotherapy, chemotherapy, hormonal blockade, and external beam radiation have the potential to enhance efficacy, overcome resistance, and reshape treatment paradigms. Theranostic-guided combinations provide a platform for personalised, multimodal cancer therapy, guided by molecular imaging and response assessment.

Scientific advances include:

• TRT + Immunotherapy: Combinations of PSMA- or FAP-directed RLT with immune checkpoint inhibitors (ICIs, e.g., anti-PD-L1) are under clinical evaluation. Early studies demonstrate increased immune cell infiltration and delayed tumour progression (Zhang J et al., 2023).
• TRT + Chemotherapy or anti-VEGF: Dual targeting of tumour and microenvironment (e.g., FAPI + bevacizumab) is being explored to achieve synergistic vascular and stromal disruption.
• Radiobiological rationale: Pairing ¹⁷⁷Lu, ²²⁵Ac, or ¹⁶¹Tb with agents modulating DNA repair, angiogenesis, or immune evasion may improve tumour cell kill and broaden the therapeutic index.
• Theranostic-guided combinations: Imaging-based patient stratification is accelerating adaptive trial designs and translational implementation.

Clinical and preclinical evidence is rapidly growing, highlighting combination strategies as one of the most promising frontiers in theranostics.