Search Results (137)

Endometriosis is a highly prevalent, chronic gynecological disorder characterized by the ectopic presence of endometrial-like tissue, driving significant morbidity and chronic pelvic pain. Pathologically, it is increasingly recognized as a fibro-inflammatory condition involving extensive tissue remodeling and fibrosis. Current conventional imaging modalities, including ultrasound and MRI, are primarily morphological, while standard molecular imaging using Positron Emission Tomography (PET) tracers has shown limited diagnostic utility. [¹⁸F]Fluorodeoxyglucose (FDG) suffers from high physiological uptake in pelvic organs and inconsistent detection of lesions. Receptor-based tracers like [⁶⁸Ga]Ga-DOTATATE have demonstrated uncertain efficacy. In contrast, radiopharmaceuticals targeting the Fibroblast Activation Protein (FAP) offer a promising molecular approach. FAP is specifically overexpressed by activated fibroblasts present in the stroma of endometriotic lesions, correlating significantly with tissue fibrosis (collagen content) and local immune infiltration (e.g., CD68 macrophages). This comprehensive review analyzes the landscape of radiopharmaceuticals for endometriosis imaging, contrasting the specific limitations of traditional metabolic and receptor agents with the molecular rationale and emerging evidence supporting the use of FAP Inhibitors (FAPI), positioning them as crucial, non-invasive tools for the future diagnosis and management of this challenging disease. Full article

Background/Objectives: Overactivation of the HGF/c-MET pathway is implicated in various cancers, making its inhibition a promising therapeutic strategy. While several MET-targeting agents are currently approved or in advanced clinical development, patient selection often relies on invasive tissue-based assays. The development of a specific c-MET radioligand for PET imaging and radioligand therapy represents a non-invasive alternative, enabling real-time monitoring of target expression and offering a pathway to personalized treatment. Methods: Radiosynthesis of [⁶⁸Ga]Ga-DOTA-EMP100 was performed using a GMP-certified ⁶⁸Ge/⁶⁸Ga generator connected to an automated synthesis module. The radiopharmaceutical production was optimized by scaling down the amount of DOTA-EMP-100 from 50 to 20 μg. Synthesis efficiency and release criteria were assessed according to Ph. Eur. for all the final products by evaluating radiochemical yield (RY%), radiochemical purity, presence of free gallium (by Radio-UV-HPLC) and gallium colloids (by Radio-TLC), molar activity (Am), chemical purity, pH, and LAL test results. Results: An optimized formulation of [⁶⁸Ga]Ga-DOTA-EMP-100, using 40 μg of precursor, provided the best outcome in terms of radiochemical performance. Process validation across three independent productions confirmed a consistent radiochemical yield of 64.5% ± 0.5, high radiochemical purity (>99.99%), and a molar activity of 53.41 GBq/µmol ± 0.8. Conclusions: [⁶⁸Ga]Ga-DOTA-EMP-100 was successfully synthesized with high purity and reproducibility, supporting its potential for multi-dose application in clinical PET imaging and targeted radioligand therapy. Full article

Background: Inflammatory bowel diseases (IBD) rely on invasive methods for detecting intestinal inflammation, with the needs for non-invasive molecular imaging tools being unmet. Integrin α4β7 is a key target in IBD pathogenesis due to its role in the recruitment of T cells. This study aimed to develop a novel ⁶⁸Ga-labeled integrin α4β7-targeted radiopharmaceutical (⁶⁸Ga-A2) and evaluate its feasibility for non-invasive PET/CT imaging of IBD inflammation in a dextran sulfate sodium (DSS)-induced murine colitis model. Methods: ⁶⁸Ga-A2 was synthesized via radiolabeling DOTA-A2 with ⁶⁸Ga. In vitro properties (radiochemical purity, stability, binding specificity, and affinity) of ⁶⁸Ga-A2 were validated. The DSS-induced colitis model was established and confirmed in C57BL/6J mice, followed by in vivo PET/CT imaging, ex vivo biodistribution studies, and histological (HE and IHC) analyses to evaluate the targeting efficacy of ⁶⁸Ga-A2. Results: ⁶⁸Ga-A2 was prepared efficiently (20 min) with a radiochemical purity of >95% and demonstrated good in vitro stability. It exhibited specific binding to integrin α4β7 with a Kd of 68.48 ± 6.55 nM. While whole-body PET/CT showed no visible inflammatory focus uptake, ex vivo imaging and biodistribution of colon tissue revealed significantly higher uptake in DSS-treated mice compared to that in healthy/blocking groups, which was consistent with histological evidence of inflammation. Conclusions: ⁶⁸Ga-A2 demonstrated specific targeting of IBD inflammatory foci in vitro and ex vivo. Despite whole-body imaging limitations, further optimization of its structure may enable it to become a promising non-invasive PET agent for IBD. These findings support future clinical investigations to validate its utility in IBD diagnosis and monitoring. Full article

Objectives: Pretargeting strategies enhance the specificity and safety of radiopharmaceuticals by separating tumor targeting from radionuclide delivery. To address the rapid clearance and systemic exposure of directly labeled small-molecule agents, a DZ-1–based pretargeting system was developed, utilizing its broad-spectrum tumor-targeting characteristics. Methods: Three DZ-TCO precursors (DZ-1-TCO, DZ-Lys-TCO, and DZ-Lys-PEG₄-TCO) were synthesized and evaluated by near-infrared fluorescence imaging in HeLa and U87MG tumor-bearing mice. Two tetrazine probes (methyl-tetrazine and mono-substituted tetrazine) were labeled with ⁶⁸Ga to yield ⁶⁸Ga-DOTA-Me-Tz and ⁶⁸Ga-DOTA-H-Tz, whose stability was assessed in PBS and serum. Pretargeted PET imaging was performed using different precursor/probe combinations and pretargeting intervals (24, 48, and 72 h). Results: All precursors exhibited tumor accumulation peaking at 24 h and signal retention up to 96 h. Both ⁶⁸Ga-DOTA-Me-Tz and ⁶⁸Ga-DOTA-H-Tz maintained >85% radiochemical stability after 4 h. PET imaging identified DZ-Lys-TCO as the most effective precursor (1.98 ± 0.72 %ID/g, T/M 3.86 ± 0.91). Using ⁶⁸Ga-DOTA-H-Tz, the 48 h interval achieved optimal uptake (3.24 ± 0.95 %ID/g) with the highest tumor-to-muscle ratio (8.30 ± 3.39). Biodistribution confirmed rapid renal clearance, low off-target accumulation, and peak tumor uptake of 3.53 ± 1.76 %ID/g (T/M 10.9 ± 0.3 at 30 min). Conclusions: The DZ-TCO/⁶⁸Ga-DOTA-Tz pretargeting system enables high-contrast tumor imaging with low background. The combination of DZ-Lys-TCO and ⁶⁸Ga-DOTA-H-Tz at a 48 h interval provides optimal performance, representing a promising platform for precise and safe radiopharmaceutical imaging. Full article

Prostate cancer (PCa) remains one of the most prevalent malignancies among men worldwide and continues to pose significant therapeutic challenges, especially in its metastatic and castration-resistant forms. Over the past two decades, the treatment paradigm has evolved from monotherapy with androgen deprivation therapy (ADT) to a multifaceted approach integrating chemotherapy, androgen receptor axis-targeted therapies (ARATs), radiopharmaceuticals, and precision medicine. This review explores the molecular underpinnings of PCa, including genetic and epigenetic alterations such as BRCA1/2, TP53, and PTEN mutations, and their role in disease progression and treatment resistance. We detail the evidence supporting the integration of systemic agents like abiraterone, enzalutamide, and darolutamide into both hormone-sensitive and castration-resistant settings. Furthermore, we highlight the expanding role of radioligand therapies, including radium-223 and Lutetium-177-labeled PSMA-617 (Lu-PSMA-617), as well as the growing impact of PARP inhibitors in genomically selected patients. The emergence of theranostic strategies and next-generation sequencing has paved the way for personalized treatment algorithms, moving toward a truly precision oncology model in PCa. This comprehensive review synthesizes current therapeutic strategies, clinical trial evidence, and future directions aimed at optimizing outcomes and quality of life for patients with advanced prostate cancer. Full article

Introduction: Platelet-derived growth factor receptor beta (PDGFRβ) is a key regulator of fibrogenesis. Non-invasive imaging of PDGFRβ expression may offer a novel approach to assess fibrotic remodeling, particularly in cardiac patients’ post-intervention, where fibrosis poses clinical risk. This study presents the GMP-compliant production of a novel PDGFRβ-targeted PET radiopharmaceutical, [⁶⁸Ga]Ga-DOTA-Z09591 ([⁶⁸Ga]Ga-ATH001), and its preclinical evaluation in mouse and human myocardial tissue, along with initial clinical imaging in patients with ST-elevation myocardial infarction (STEMI). Methods: The precursor was chemically synthesized and radiolabeled with gallium-68 using a fully automated, GMP-compatible system and a pharmaceutical-grade ⁶⁸Ge/⁶⁸Ga generator. Autoradiography, H&E, Sirius Red, Masson’s trichrome, and IHC staining were performed on infarcted mouse hearts and human myocardial biopsies. In vivo PET/MRI with [⁶⁸Ga]Ga-ATH001, ¹⁵O-H₂O, and gadolinium contrast was conducted in STEMI patients one week post-percutaneous coronary intervention. Results: [⁶⁸Ga]Ga-ATH001 was produced with high radiochemical yield and purity. Autoradiography demonstrated specific, receptor-mediated binding of [⁶⁸Ga]Ga-ATH001, co-localizing with PDGFRβ immunoreactivity, collagen deposition, and tissue damage. In STEMI patients, focal tracer uptake was observed in infarcted myocardium correlating with MRI-detected structural abnormalities and perfusion defects on ¹⁵O-H₂O PET. Uptake in unaffected myocardium was low and homogeneous, consistent with minimal physiological PDGFRβ expression. Conclusions: [⁶⁸Ga]Ga-ATH001 was successfully developed and validated for phase 0 clinical study. The tracer demonstrated PDGFRβ-specific binding in human fibrotic myocardium and enabled non-invasive detection of myocardial fibrogenic activity in STEMI patients. These findings support further clinical evaluation of [⁶⁸Ga]Ga-ATH001 as a targeted molecular imaging agent for early assessment of post-infarction fibrosis. Full article

Radiopharmaceutical development usually requires chelators to route radiometals to specific cancer targets. However, there is no universal chelator. To reduce off-target side effects, new chelators are needed as the radiometal toolset grows. DOTA is the most often used chelator for radiometals in radiopharmaceutical development, however DOTA’s extreme conditions make it unsuitable for labeling heat sensitive biological vectors. The ideal chelator should be thermodynamically and kinetically stable, allowing labeling under mild conditions (~37 °C). In recent years, new hybrid chelators with enhanced characteristics have emerged, warranting further investigation for medical applications. This paper aims to discuss some of these promising chelators. Full article

Metastatic or unresectable pheochromocytomas and paragangliomas (PPGLs) remain rare but clinically challenging neuroendocrine neoplasms with limited curative options. Traditionally managed with surgery, radionuclide therapy, or cytotoxic chemotherapy, systemic treatments have historically achieved disease stabilization, rather than durable remissions. In recent years, however, the therapeutic landscape has evolved substantially. Radiopharmaceuticals such as ¹³¹I-MIBG and ¹⁷⁷Lu-DOTATATE continue to play a pivotal role, achieving disease control in many patients. Cytotoxic regimens, particularly temozolomide, remain relevant, with some studies suggesting that SDHB-mutated PPGLs demonstrate a heightened sensitivity associated with MGMT promoter hypermethylation and reduced MGMT expression. Targeted agents are increasingly important: multi-kinase inhibitors such as sunitinib, anlotinib, and cabozantinib have shown meaningful activity. The landmark approval of belzutifan, a HIF-2α inhibitor, in 2025 represents the first oral targeted therapy for advanced/metastatic PPGL, which is particularly relevant for pseudohypoxic Cluster 1 tumors. Immunotherapy has yielded modest responses with checkpoint inhibitor monotherapy, but ongoing studies of dual checkpoint blockade and TKI–ICI combinations hold promise. Novel approaches, including PARP inhibition, metabolic targeting strategies, and cancer vaccines, are under investigation, especially for aggressive SDHB-related disease. Optimal sequencing of these therapies is emerging as a central challenge, with treatment strategies increasingly tailored to molecular genotype, tumor behavior, and functional imaging phenotype. This review summarizes current evidence and highlights ongoing clinical trials, underscoring a paradigm shift toward precision medicine and rational combination strategies. Collectively, these advances bring cautious optimism that metastatic PPGLs may soon become a more manageable chronic disease with improved survival and quality of life. Full article

Radioligand therapy (RLT) is a targeted treatment modality that combines a tumour-specific ligand with a therapeutic radionuclide. Once administered, the radiopharmaceutical binds selectively to cancer-associated targets, delivering cytotoxic radiation directly to tumour cells while sparing surrounding tissues. Two RLT agents, [¹⁷⁷Lu]Lu-DOTA-TATE (Lutathera^®) and [¹⁷⁷Lu]Lu-PSMA-617 (Pluvicto^®), have received regulatory approval for the treatment of advanced gastroenteropancreatic neuroendocrine tumours and metastatic castration-resistant prostate cancer, respectively. As of July 2025, more than 400 clinical trials are registered, exploring novel molecular targets such as FAP, CAIX, and GRPR, as well as alternative radionuclides and combination regimens in both solid and haematologic malignancies. In this review, we describe the design principles and mechanisms of action of RLT, summarise clinical evidence for approved and emerging radiopharmaceuticals, and discuss current global disparities in access and availability. Finally, we outline the main clinical challenges, including fixed dosing regimens, resistance, toxicity, and variability in patient selection and response assessment. Continued research to optimise radiopharmaceutical design, together with investment in infrastructure, workforce capacity, and international collaboration, will be essential to expand access and realise the full potential of RLT as a leading treatment strategy in modern oncology. Full article

This review comprehensively assesses the clinical applications and future potential of alpha-emitting radionuclides available for targeted alpha-particle therapy (TAT) in cancer treatment. The approval of radium-223 therapy in 2013 marked a significant advancement in alpha-emitting therapeutic radiopharmaceuticals, which are primarily used in treatment of prostate cancer. The EU SECURE project was introduced as a major initiative to enhance the sustainability and safety of medical alpha-emitting radionuclides production in Europe. This literature review was conducted by a multidisciplinary team on selected radionuclides, including actinium-225, bismuth-213, astatine-211, lead-212, terbium-149, radium-223 and thorium-227. These were selected based on their clinical significance, as identified in the EU PRISMAP project and subsequent literature searches. The review process involved searching major databases using specific keywords related to alpha-emitter therapy and was limited to articles in English. For each selected radionuclide, the physical characteristics, the radiochemistry, and the pre-clinical and clinical studies are explored. Actinium-225 is the most widely studied alpha emitter, with several preclinical and clinical studies on prostate cancer and neuroendocrine tumours. Other types of tumours (such as glioblastoma) still require preclinical and clinical development. Bismuth-213 bound to antibodies, peptides and nanobodies has shown optimal results in preclinical and clinical studies, with increased median survival and no significant toxicity. Astatine-211 differs from most other α-emitters relevant to TAT, since it yields one α-particle per decay. This offers certain translational advantages, including the simplification of radiation dosimetry calculations and quality control (QC). Lead-212 has the advantage of being an in situ generator with likely widespread availability. Although clinical data are limited, the findings are promising at this stage. The unconventional production of Terbium-149 is the primary reason it has not yet progressed to clinical trials. Overcoming this production obstacle would allow more detailed preclinical investigations. Optimal results with Thorium-227-labelled agents have been observed in preclinical studies, including delays in cellular growth, multiple double-strand breaks and complete regression. Intermediate phase I trial results have also been reported, demonstrating safety and tolerability, as well as an objective response rate of 25%.: The results highlight the advantages of alpha particles in targeting cancer cells with minimal radiation to normal tissue, emphasising the need for high specificity and stability in delivery mechanisms, as well as suggesting that the full clinical potential of alpha particle therapy remains unexplored. Theranostic approach and dosimetric evaluations still represent relevant challenges. Full article

Lapatinib is an approved therapeutic agent for the treatment of HER2-positive breast cancer. It has a high affinity for the non-receptor cytoplasmic tyrosine kinases of the EGFR and HER2 receptors. It is a type II inhibitor, with K_i^app values of 3 nM and 13 nM, respectively. The dissociation rate of the lapatinib–receptor complex is notably slow compared with many other kinase inhibitors. Although the literature contains numerous reports on radiolabelled ligands for HER-family receptors, studies on radiolabelled tyrosine kinase inhibitors are far fewer, and only few focus specifically on radiolabelled lapatinib. The aim of this review is to compile and discuss the chemical and biological data on lapatinib-based radiopharmaceuticals with potential applications in the diagnosis and treatment of HER2-positive tumours. Full article

Alzheimer’s disease (AD) is the most common cause of dementia worldwide, and there are still no strategies to slow or prevent its clinical progression. Significant financial and research resources have been invested into studying the pathology of AD. However, its pathogenesis is not fully understood. This review provides a comprehensive analysis of current understanding of AD pathogenesis, including classical hypotheses (amyloid cascade, tau pathology, neuroinflammation, oxidative stress), emerging mechanisms (cellular senescence, endoplasmic reticulum stress, ubiquitin-proteasome system dysfunction), and alternative mechanisms (cholinergic dysfunction, glutamate excitotoxicity, disruption of the microbiota–gut–brain axis, and autophagy). Schematic illustrations summarize the relationships between the hypotheses and their role in the pathogenesis of AD. Particular attention is paid to the systematization of promising biological targets and the analysis of modern ligands of various nature, including small molecules, peptides, antibodies and their fragments, natural compounds, as well as innovative hybrid and multifunctional structures. A separate section is devoted to radiopharmaceuticals for PET imaging (Florbetaben, Flortaucipir, etc.) and promising therapeutic agents. Thus, in this review we (1) systematize modern concepts of AD pathogenesis, including classical, emerging mechanisms and alternative hypotheses; (2) conduct a comparative analysis of ligand classes (small molecules, peptides, antibodies, etc.) and their therapeutic potential; and (3) discuss the clinical prospects of radiopharmaceuticals for PET imaging and targeted therapy. The work provides a comprehensive analysis of modern approaches, which can help in the development of more effective drugs against AD. Full article

Alpha therapy (TAT) relies on combining alpha-emitting radionuclides with specific cell-targeting vectors to deliver a high payload of cytotoxic radiation capable of destroying tumor tissues. TAT efficacy comes from the tissue selectivity of the targeting vector, the high linear energy transfer (LET) of the radionuclide, and the short range of alpha particles in tissues. Recent research studies have been directed to evaluate TAT on a preclinical and clinical scale, including evaluating damage to tumor tissues with minimal toxic radiation effects on surrounding healthy tissues. This review highlights the use of Actinium-225/Bismuth-213 radionuclides as promising candidates for TAT. Herein, we begin with a discussion on the production and supply of [²²⁵Ac]Ac/[²¹³Bi]Bi followed by the formulation of [²²⁵Ac]Ac/[²¹³Bi]Bi-radiopharmaceuticals using different radiolabeling techniques. Finally, we have summarized the preclinical and clinical evaluation of these potential radiotheranostic agents. Full article

The integration of nanotechnology into drug repurposing strategies is redefining the development landscape for diagnostic, therapeutic, and theranostic agents. In radiopharmacy, nanoplatforms are increasingly being explored to enhance or extend the use of existing radiopharmaceuticals, complementing earlier applications in other biomedical fields. Many of these nanoplatforms evolve into multifunctional systems by incorporating additional imaging modalities (e.g., MRI, fluorescence) or non-radioactive therapies (e.g., photodynamic therapy, chemotherapy). These hybrid constructs often emerge from the reformulation, repositioning, or revival of previously approved or abandoned compounds, generating entities with novel pharmacological, pharmacokinetic, and biodistribution profiles. However, their translational potential faces significant regulatory hurdles. Existing frameworks—typically designed for single-modality drugs or devices—struggle to accommodate the combined complexity of nanoengineering, radioactive components, and integrated functionalities. This review examines how these systems challenge current norms in classification, safety assessment, preclinical modeling, and regulatory coordination. It also addresses emerging concerns around digital adjuncts such as AI-assisted dosimetry and software-based therapy planning. Finally, the article outlines international initiatives aimed at closing regulatory gaps and provides future directions for building harmonized, risk-adapted frameworks that support innovation while ensuring safety and efficacy. Full article

Albumin-binding agents enhance tumor uptake of radiopharmaceuticals targeting prostate-specific membrane antigens (PSMAs) in radiotherapy. We synthesized PSMA-NARI-56, a molecule with both PSMA targeting activity and albumin-binding moiety, labeled with ¹⁷⁷Lu as the therapeutic agent. The aim of this study was to determine the specific binding of ¹⁷⁷Lu-PSMA-NARI-56 towards PSMA, assess its biodistribution, and evaluate therapeutic effectiveness by tumor-bearing mice. The effect of ¹⁷⁷Lu-PSMA-NARI-56 viability of PSMA-positive cell (LNCaP) was evaluated. Biodistribution and endoradiotherapy studies were utilized to determine the distribution, targeting, and anti-tumor efficacy by tumor-bearing mice identified by ¹¹¹In-PSMA-NARI-56. ¹⁷⁷Lu-PSMA-NARI-56 exhibited a significant impact on the viability of the LNCaP cell. Biodistribution results revealed the maximum tumor uptake of ¹⁷⁷Lu-PSMA-NARI-56 occurring within 24 h, reaching 40.56 ± 10.01%ID/g. In radionuclide therapy, at 58 days post-injection (p.i.), ¹⁷⁷Lu-PSMA-NARI-56 demonstrated superior tumor inhibition (98%) compared to ¹⁷⁷Lu-PSMA-617 (58%), and the mouse survival rate after 90 days of radiotherapy (90%) was also higher than that of ¹⁷⁷Lu-PSMA-617 (30%) in LNCaP tumor-bearing mice. In the PSMA-positive animal model, ¹⁷⁷Lu-PSMA-NARI-56 shows higher potential radiotheranostic and prolonged accumulation (identify by ¹¹¹In-PSMA-NARI-56/nanoSPECT/CT image), offering the potential for improved treatment effectiveness and increased survival rates when compared to ¹⁷⁷Lu-PSMA-617. Full article