Search Results (621)

Background: Actinium-225 (²²⁵Ac) is receiving major attention as the radionuclide of choice for targeted alpha therapy (TAT) due to its outstanding physical properties such as a long physical half-life of 9.9 days and a short range of alpha (α)-particles which are responsible for the destruction of malignant tumors, whilst sparing normal surrounding tissues. Although the physical properties of ²²⁵Ac make it a desirable radionuclide for TAT, its application is challenging due to the lack of chelators available to stabilize its daughter radionuclides, resulting in the recoil effect. This occurs when there is a breakdown between the radionuclide and the chelator, therefore minimizing the therapeutic effects of the radiopharmaceutical. Nanodrug delivery systems (NDDSs) may minimize the challenge of ²²⁵Ac’s recoiling daughters and increase tumor penetration. Aim: This study aimed at using poly(lactic-co-glycolic)acid (PLGA) and chitosan (CS) nanoparticles as a delivery vehicle for targeted alpha therapy of prostate cancer in order to increase the therapeutic effect of ²²⁵Ac PSMA617-TFA. Methods and Results: PLGA nanoparticles were prepared using a nanoprecipitation method, after which they were functionalized with chitosan and folic acid. Following synthesis of ²²⁵Ac PSMA617-TFA, the radiopharmaceutical was loaded onto the nanoparticles. SEM analysis and FTIR were performed for characterization of the nanoparticles, and in-vitro drug release of ²²⁵Ac PSMA617-TFA at pH = 6.5 and pH = 7.4, respectively, was measured. The nanoparticles prepared had an average size of 200 nm and had a positive charge. This was further confirmed using a zetasizer and with scanning electron microscope (SEM) analysis. The PLGA-CS nanoparticles indicated a high encapsulation efficiency after 24 h. The results also showed a controlled release of ²²⁵Ac PSMA617-TFA over 72 h. The results of this study indicate that PLGA-CS nanoparticles are suitable for retaining ²²⁵Ac and its recoiling daughters (²²¹Fr and ²¹³Bi) at the tumor site, potentially providing a platform for future therapeutic evaluation. Conclusions: The results of this study indicate that PLGA-CS nanoparticles demonstrate feasibility as a drug delivery vehicle for ²²⁵Ac PSMA617-TFA, with effective retention of ²²⁵Ac and its decay daughters. However, biological validation through in vitro cellular studies and in vivo preclinical models is required before therapeutic effectiveness can be established. Full article

Neuroendocrine neoplasms (NENs) are a heterogeneous family of tumors that have traditionally been regarded as “immune cold” and largely refractory to PD-1/PD-L1 checkpoint blockade, with notable exceptions such as Merkel cell carcinoma (MCC). The advent of single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics has enabled unprecedented dissection of the NEN tumor microenvironment (TME), but a cross-subtype synthesis is lacking. This review aims to integrate single-cell and spatial transcriptomic findings across major NEN subtypes to reframe NEN immunosuppression and delineate translational implications. To this end, we performed a structured narrative review of PubMed-indexed studies up to 30 April 2026, prioritizing original human scRNA-seq, single-nucleus RNA-seq, spatial transcriptomic, and spatial proteomic studies of NENs, supplemented by mechanistic, clinical, and biomarker-focused reports providing essential context. Across these studies, synthesis spanning pancreatic, pulmonary, gastrointestinal, cutaneous, pituitary, adrenal, and other NEN subtypes highlights conserved features beyond the PD-1/PD-L1 axis, including myeloid-dominated infiltration with alternative checkpoints (VISTA, TIM-3, Galectin-9), cancer-associated fibroblast-mediated immune exclusion, lineage-state-dependent immune visibility, and direct immunomodulation by neuroendocrine secretory products such as calcitonin gene-related peptide. We propose a four-layer framework integrating these mechanisms and linking them to emerging biomarkers and therapies, including DLL3-directed bispecifics, alternative checkpoint inhibitors, stromal-targeting agents, and peptide receptor radionuclide therapy combinations. Together, these findings indicate that single-cell and spatial transcriptomic studies reframe NEN immunosuppression as a multilayered, subtype-dependent process, providing a conceptual scaffold for biomarker-guided, subtype-adapted therapeutic strategies and prospective clinical trial design in neuroendocrine oncology. Full article

Yttrium-90 (⁹⁰Y) is a pivotal pure beta-emitting radionuclide extensively employed in the targeted therapy of malignant tumors, such as hepatocellular carcinoma and lymphoma. The ⁹⁰Sr-⁹⁰Y generator system represents the most effective method for producing no-carrier-added (NCA) ⁹⁰Y to meet escalating clinical demands. However, safe clinical application necessitates the stringent separation of its parent isotope, ⁹⁰Sr, which poses significant radiotoxicological risks due to its long half-life and bone-seeking behavior. This review comprehensively summarizes recent advances in solid-phase adsorbent materials developed for the high-efficiency separation of Y³⁺ and Sr²⁺. We systematically analyze the design strategies, molecular recognition mechanisms, and performance evaluation metrics of various functional systems. Key materials discussed include extraction chromatography (EXC) resins based on organophosphorus extractants, diglycolamide (DGA) derivatives, and crown ethers, as well as inorganic ion exchangers such as antimony-based materials, manganese oxides, and zeolite-like molecular sieves. Special attention is given to composite modification strategies, including silica-based and polymer-matrix composites, and metal doping techniques aimed at enhancing radiation resistance, acid stability, and Sr-Y separation factors (SF). Finally, we provide an outlook on the future development of next-generation ⁹⁰Sr-⁹⁰Y generator materials, highlighting the imperative of transitioning from idealized simulated environments to robust, field-ready applications. Full article

Lutetium-177-PSMA-617 (Lu-PSMA) radioligand therapy (RLT) is established in metastatic castration-resistant prostate cancer (mCRPC), with regulatory approvals based on the VISION and TheraP trials. Subsequent trials have extended the evidence to taxane-naive mCRPC (PSMAfore) and demonstrated that combining Lu-PSMA with enzalutamide yields a significant overall survival benefit over enzalutamide alone (ENZA-p). However, higher and more homogeneous PSMA expression in treatment-naive disease, combined with lower tumor burden and preserved bone marrow reserve, provides a biological rationale for deploying RLT earlier in the disease course. In metastatic hormone-sensitive prostate cancer (mHSPC), the Phase III PSMAddition trial reported improved radiographic progression-free survival when Lu-PSMA was added to standard androgen deprivation therapy (ADT) plus androgen receptor pathway inhibitor (ARPI), and the Phase II UpFrontPSMA trial demonstrated enhanced biochemical responses with Lu-PSMA induction before docetaxel. In oligometastatic and oligorecurrent disease, the BULLSEYE and LUNAR trials have shown progression-free survival benefits, raising the possibility of deferring androgen deprivation therapy and its associated morbidity. Meanwhile, next-generation radionuclides, including actinium-225 (WARMTH) and the dual beta-Auger emitter terbium-161 (VIOLET), are entering clinical development to address the radiobiological limitations of Lutetium-177. This review synthesizes the evidence for PSMA-targeted radioligand therapy across the prostate cancer disease continuum and discusses patient selection, treatment sequencing, and the access and cost-effectiveness considerations that will shape adoption in earlier disease settings. Full article

Prostate-specific membrane antigen (PSMA) has become a central molecular target in prostate cancer because it enables both high-performance imaging and targeted radioligand therapy. PSMA positron emission tomography/computed tomography (PET/CT) is now used across several clinical settings, including primary staging of higher-risk localized disease, localization of biochemical recurrence, salvage radiotherapy planning, and assessment of oligometastatic disease. In metastatic castration-resistant prostate cancer, PSMA-targeted radioligand therapy (RLT), particularly lutetium-177-labeled PSMA-617, has established therapeutic value and is moving into earlier disease states. From an applied science perspective, the clinical performance of PSMA theranostics depends not only on target expression and trial efficacy, but also on radiopharmaceutical design, radionuclide selection, radiochemical quality, PET acquisition and reconstruction, standardized reporting, dosimetry, and quantitative response assessment. This narrative review summarizes the biological, radiochemical, and technical foundations of PSMA theranostics, the clinical evidence supporting PSMA PET/CT in key disease states, and the pivotal data for PSMA-targeted RLT. It also discusses imaging-based treatment eligibility, dosimetry, post-therapy imaging, Response Evaluation Criteria in PSMA Imaging, and next-generation beta- and alpha-emitting platforms. PSMA theranostics should be understood as an integrated clinical and technological platform that links molecular imaging, treatment selection, radionuclide delivery, and longitudinal response assessment across the prostate cancer care pathway. Full article

Background/Objectives: Poly (ADP-ribose) polymerase (PARP), particularly PARP-1, is overexpressed in prostate cancer and linked to poor prognosis. PARP inhibitors show efficacy in homologous recombination deficiency (HRD)-positive tumors, but 30–70% of patients develop resistance, often due to low PARP expression. Tissue biopsies have limitations in assessing PARP levels, highlighting the need for noninvasive imaging tools. This study aimed to develop a novel [⁶⁸Ga]Ga-PARP-targeted radiotracer for prostate cancer visualization and therapy monitoring, with potential implications for targeted radionuclide therapy. Methods: PET/CT imaging was conducted in 22RV1 prostate cancer xenograft-bearing mice using the [⁶⁸Ga]Ga-FL9-7 probe. Imaging was performed at 1, 2, and 3 h post-injection. Standardized uptake values (SUV) were quantified to evaluate tumor and organ uptake, and tumor-to-normal tissue (T/NT) contrast ratios were calculated. Results: [⁶⁸Ga]Ga-FL9-7 rapidly accumulated in tumors, with optimal imaging contrast achieved at 3 h post-injection. Normal organ uptake (e.g., kidneys) peaked at 1 h and subsequently declined, while tumor uptake increased over time. This differential clearance and retention resulted in the highest T/NT ratio at the 3 h time point. Conclusions: The [⁶⁸Ga]Ga-FL9-7 probe enables effective noninvasive visualization of PARP-1 expression in prostate cancer, demonstrating clinical potential for tumor localization and monitoring of PARP-targeted therapies. This work also lays the groundwork for further development of PARP-targeted radionuclide therapy strategies. Full article

The fibroblast activation protein (FAP) has emerged as a compelling theranostic target because it is highly expressed in the tumour microenvironment of many solid malignancies, predominantly on cancer-associated fibroblasts and, in selected tumour types, also on tumour cells. Following the rapid clinical expansion of FAP-targeted PET imaging, FAP-targeted radionuclide therapy (FAP-TRT) is now being explored as a predominantly stromal-directed therapeutic strategy across a broad range of solid malignancies. However, unlike established theranostic paradigms, such as prostate-specific membrane antigen- and somatostatin receptor-directed radioligand therapies, FAP-TRT faces distinct biological and translational challenges, including stromal heterogeneity, variable patterns of FAP expression, and limited tumour retention of many early radioligands. This review outlines the biological rationale, mechanistic basis, radiopharmaceutical development, and emerging clinical evidence for FAP-TRT. We highlight the recent ligand-engineering strategies aimed to improve tumour residence time and absorbed dose, and to summarise the current clinical data with particular focus on dosimetry, safety, and early efficacy signals. We also discuss key future directions, including disease-focused clinical development and rational combination strategies with immune checkpoint inhibitors, DNA damage response inhibitors, and chemotherapy. Overall, the available data support the feasibility of FAP-TRT but also underscore the need for improved ligand design and biologically informed clinical development to define its role within the evolving theranostic landscape. Full article

Background/Objectives: Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor that often expresses somatostatin receptors (SSTRs). While various PET radiopharmaceuticals were used, there is no universal consensus on the optimal imaging modality for whole-body assessment of MTC. This study aims to evaluate the detection rate (DR) and clinical management impact of SSTR PET/CT imaging in patients with MTC. Methods: A systematic search was conducted across PubMed/MEDLINE, Scopus, and Embase. A total of 14 studies (comprising 350 patients) were eligible for quantitative meta-analysis. Pooled DRs were calculated using a random-effects model, and methodological quality was assessed via the QUADAS-2 tool. Results: Our analysis revealed an overall DR of 75.1% (95% CI: 67.6–82.6%) for recurrent or metastatic MTC, showing moderate significant heterogeneity (I² = 65.41%). Clinical impact of SSTR PET/CT was demonstrated in 16.6–100% of cases, primarily by identifying candidates for Peptide Receptor Radionuclide Therapy. Only a few studied investigated the relationship between serum calcitonin levels and the detection rate of SSTR PET/CT, finding a significant correlation. Conclusions: The DR of SSTR PET/CT in recurrent/metastatic MTC was high. SSTR PET/CT may have a positive impact on clinical management in a significant number of cases. Full article

Background: Neuroendocrine tumors—are relatively rare but increasingly diagnosed malignancies originating from diffuse neuroendocrine cells, most commonly affecting the gastroenteropancreatic system. Due to their long asymptomatic development and low incidence, pose a diagnostic and therapeutic challenge for physicians. Recently, the role of nuclear medicine has been growing not only in the diagnostic stage but also in treatment. Systemic radionuclide therapy using somatostatin analogs labelled with the radioisotope lutetium-177 is becoming increasingly common in patients with advanced-stage disease. Currently, most patients receive a standard activity of therapeutic radiopharmaceuticals. Recent clinical studies provide increasing evidence of a close relationship between the absorbed radiation dose in pathological lesions and the therapeutic effect of radioisotope therapy. Internal dosimetry is used to measure the doses of ionising radiation absorbed by the patient after administration of the radiopharmaceutical. The lack of individual internal dosimetry prior to therapy means that only a small fraction of patients receive optimal doses of radioactivity, which is markedly different from external beam radiotherapy planning. Methods: A narrative literature review was conducted using the PubMed/MEDLINE and Embase databases, focusing primarily on publications from the last years. The search strategy included combinations of keywords related to peptide receptor radionuclide therapy and dosimetry, such as “Lutetium-177”, “neuroendocrine tumors”, “dosimetry”, “PRRT”, “systemic radionuclide therapy” and “artificial intelligence”. Particular emphasis was placed on recent prospective clinical studies, multicenter investigations, systematic reviews and consensus documents published by major nuclear medicine societies, including the European Association of Nuclear Medicine (EANM) and the Society of Nuclear Medicine and Molecular Imaging (SNMMI). Seminal earlier publications considered essential for understanding the development of dosimetry concepts and clinical implementation were also included. Results: This study confirms the existence of a clinically significant dose-response relationship in ¹⁷⁷Lu-PRRT. Higher absorbed doses to tumour lesions are associated with longer progression-free survival. The lack of individualized internal dosimetry prior to therapy means that only a small proportion of patients receive optimal radiation doses. Simplified dosimetric approaches with a reduced number of imaging time points, together with emerging artificial intelligence–based tools, appear promising for reducing the complexity of the dosimetry process. Conclusions: The aim of this study was to analyse the current literature on the role of internal dosimetry in the treatment of neuroendocrine tumors using the radioisotope lutetium-177. Available data support the clinical relevance of individualized dosimetry and highlight its potential to optimize both therapeutic efficacy and treatment safety. Full article

²¹²Pb is an important medical radionuclide for targeted alpha therapy, and its reliable supply depends on the efficient production of parent nuclides such as ²²⁸Ra, ²²⁸Th, and ²²⁴Ra. Natural thorium resources are abundant and represent a potential source of these radionuclides. However, the separation and enrichment of trace radium from thorium-rich high-salinity systems remain challenging due to extremely low radium concentrations and Th/Ra mass ratios on the order of 10⁹. In this work, a radium separation strategy based on BaSO₄ co-precipitation was developed. The precipitation behavior of BaSO₄, precipitation kinetics, radium co-precipitation efficiency, and thorium recovery in concentrated thorium nitrate solutions were systematically investigated. The results show that elevated ionic strength and competitive interactions between Th⁴⁺ and SO₄²⁻ reduce the effective sulfate activity under high-thorium conditions, making excess sulfate necessary to achieve efficient BaSO₄ precipitation. Under optimized conditions, the radium co-precipitation recovery exceeded 80% at a Ba²⁺ concentration of 3 mM. Meanwhile, thorium exhibited negligible incorporation into the BaSO₄ phase and could be almost completely recovered via subsequent hydroxide precipitation. The proposed method features operational simplicity, use of common reagents, low cost, and compatibility with high-salinity matrices. It provides a feasible technical pathway for the subsequent production of high-purity ²²⁸Th or ²²⁴Ra and the preparation of ²²⁸Th/²¹²Pb or ²²⁴Ra/²¹²Pb generator systems. Full article

In medicine, nanoparticles are used for various purposes, including theranostics, imaging, diagnostics, drug delivery, tissue regeneration and targeted cancer treatments, and to minimize the harmful side effects associated with conventional therapies. Target-specific biomolecules, such as silica nanoparticles (SiNPs) labeled with metallic radionuclides, are becoming increasingly popular. The choice of radionuclide is based on its nuclear properties. Silica has several advantages for nanoparticle synthesis, including high biocompatibility, the capacity for drug encapsulation due to its porous structure, and the potential for extensive surface functionalization, including radiolabeling for imaging and therapeutic applications. A radionuclide can be attached to a silica nanoparticle either directly or through the use of chelators or polymers. Additionally, the capability to encapsulate therapeutic agents within such systems offers significant potential for the development of targeted therapies. This study aims to provide a comprehensive overview of recent developments in the radiolabeling of silica-based nanoparticles, with a focus on their application in nuclear medicine, particularly in diagnostic imaging and targeted radionuclide therapy. Theranostics employs a range of imaging modalities to guide and monitor therapeutic interventions. Principal techniques include positron emission tomography (PET), single-photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), and Optical Imaging (such as fluorescence and bioluminescence). These imaging methods enable precise visualization of pathological sites, facilitate tracking of therapeutic agent distribution, and permit real-time assessment of treatment efficacy. Full article

Radiometabolic therapy is a mechanistically plausible but clinically underused strategy in lymphoma. Its rationale is based on the selective delivery of cytotoxic radiation to malignant lymphoid cells through antibodies, peptides, or small molecules directed against tumor-associated targets. Radioimmunotherapy with anti-CD20 agents, including 90Y-ibritumomab tiuxetan and 131I-tositumomab, demonstrated meaningful efficacy in B-cell non-Hodgkin lymphoma, particularly in indolent and relapsed/refractory settings. However, despite encouraging clinical results, its use progressively declined because of logistical, regulatory, commercial, and multidisciplinary barriers. More recently, renewed interest has emerged with the development of novel antibody–radionuclide conjugates and radioligand-based theranostic strategies targeting CD22, CD37, CD45, and CXCR4. Among these, CXCR4-directed imaging and therapy with 68Ga-pentixafor and 177Lu/90Y-pentixather illustrate image-guided patient selection and targeted radionuclide treatment in advanced hematologic malignancies. This narrative review summarizes evidence retrieved from Scopus and PubMed on radiometabolic therapy in lymphoma, with particular attention paid to established radioimmunotherapy, emerging targets, radioligand therapy, dosimetry, toxicity, and combination strategies with chemotherapy, immunotherapy, and hematopoietic stem cell transplantation. Available evidence supports the plausibility and possible clinical utility of these approaches, but remains heterogeneous and, for several newer targets, preliminary. Future development will require prospective trials, standardized imaging-based selection, individualized dosimetry, and integration within multidisciplinary lymphoma treatment pathways. Full article

Background: Neuroendocrine tumours (NETs) are heterogeneous neoplasms with several treatment options. Response rates, disease progression, and haematological toxicities can limit the use of some indicated treatments. Case Presentation: A 73-year-old woman with a well-differentiated grade 2 pancreatic NET (Ki-67 18%) underwent surgical resection and later developed hepatic recurrence. First-line treatment with sunitinib plus octreotide achieved temporary disease stabilisation. Upon progression, peptide receptor radionuclide therapy (PRRT) with ¹⁷⁷Lu-DOTATATE was initiated, resulting in stable disease but complicated by grade 3 thrombocytopenia. Two years later, PRRT retreatment was performed due to disease progression, which led to grade 4 thrombocytopenia. Further treatments with capecitabine and everolimus were limited by progression and significant thrombocytopenia. Therapy was switched to streptozocin plus 5-fluorouracil, which resulted in recovery of platelet counts, absence of haematological toxicity, and a sustained radiologic response until March 2025, when she presented with hepatic progression. FOLFOX chemotherapy was initiated but discontinued after one cycle due to severe thrombocytopenia. Deterioration in general condition ultimately led to supportive care and death in March 2026. Conclusions: This case highlights the risk of cumulative haematological toxicity with PRRT, particularly in retreatment settings. Careful patient selection and close monitoring are essential. Streptozocin-based chemotherapy may be an effective and well-tolerated alternative for patients with treatment-limiting toxicity. Full article

Background: Radioiodine (Na[¹³¹I]I) therapy is the cornerstone of systemic treatment for differentiated thyroid cancer (DTC), exploiting sodium–iodide symporter (NIS) expression for durable control. Up to 30–40% of advanced cases develop radioiodine-refractory disease (RAI-R DTC), marked by impaired iodine uptake, aggressive behavior, and poor response to Na[¹³¹I]I. Locoregional treatments, multikinase inhibitors (MKIs), and selective targeted agents improve progression-free survival but are not curative and carry cumulative toxicity, motivating precision-based alternatives. The primary objective of this review is to clarify the evolving theranostic paradigm in RAI-R DTC; the secondary objectives are to appraise redifferentiation and iodine-based theranostics for restoring or exploiting iodine avidity and to evaluate non-iodine theranostic strategies for cases where iodine biology is absent, impaired, or unreliable. Methods: This narrative review synthesizes contemporary evidence on theranostic strategies in RAI-R DTC, drawn from available studies, clinical trials, and current guidelines, with an emphasis on redifferentiation and non-iodine approaches; a systematic search protocol was not applied. Results: Theranostics couples target-specific molecular imaging with matched radionuclide therapy and response-adapted sequencing. Its most transformative application is redifferentiation, in which pharmacologic modulation of oncogenic signaling can restore iodine avidity and enable renewed, dosimetry-guided Na[¹³¹I]I treatment. Beyond iodine, somatostatin receptor (SSTR) imaging and peptide receptor radionuclide therapy (PRRT) have re-emerged in very selected cases, whereas alpha emitters remain investigational. Refractoriness is increasingly viewed as a reversible continuum rather than a fixed state. Conclusions: Theranostics can individualize RAI-R DTC treatment, restoring or exploiting iodine biology where possible and shifting to non-iodine targets where it is unreliable. Patient selection, timing, and integration with systemic therapy are central, and prospective validation is needed. Full article

Radiolabelled nanoparticles are increasingly investigated as multifunctional platforms for cancer imaging, biodistribution tracking, dosimetry, and radionuclide-based therapy. This review focuses on three representative inorganic nanoplatforms: zinc oxide (ZnO), iron oxide-based, and gold (Au) nanoparticles. These systems were selected because they combine distinct physicochemical properties with versatile surface engineering and radiolabelling strategies. ZnO nanoparticles offer pH-responsive behaviour and drug-delivery potential; iron oxide-based nanoparticles provide magnetic functionality, Magnetic resonance imaging (MRI) compatibility, and opportunities for magnetic hyperthermia or local nanobrachytherapy; and Au nanoparticles enable stable surface functionalization, radiometal chelation, radiosensitisation, photothermal effects, and alpha or beta-emitter-based local therapy. The review critically discusses synthesis and surface-modification methods, chelator-mediated and chelator-free radiolabelling, coating-assisted and anchoring-mediated strategies, and the influence of these factors on radiochemical stability, biodistribution, tumour uptake, therapeutic response, toxicity, and clearance. A function-based comparison of the reviewed studies highlights that many systems demonstrate efficient radiolabelling and imaging capability, whereas fewer provide direct in vivo therapeutic efficacy, long-term toxicity, or metabolic clearance data. Overall, radiolabelled ZnO, iron oxide-based, and Au nanoparticles show strong potential for cancer theranostics, tumour-to-organ distribution, therapeutic benefit, and safety. Full article