Search Results (383)

Evaluating the productivity contribution of individual fracturing stages in deep coalbed methane (CBM) horizontal wells remains a critical challenge, hindering the optimization of stimulation designs. This study systematically integrates dual-phase (aqueous and gaseous) fracturing tracer monitoring with machine learning algorithms to address this issue. Based on large-scale field applications across ten deep CBM horizontal wells in the Changqing mining area of the Ordos Basin, comprising 132 monitored stages, quantitative production profile data were interpreted. Three distinct gas production archetypes—Homogeneous, Heel-Dominated, and Heterogeneous—were identified, each governed by specific geomechanical and stratigraphic controls. Pearson correlation analysis and Random Forest feature importance ranking were employed to decouple the hierarchical influence of geological parameters (Class I coal intersection length, trajectory position, coal thickness) and engineering parameters (proppant volume, pumping rate, fluid volume). A power-law correlation between Class I coal length and initial gas productivity was quantified (R² = 0.71). For the first time, an economically viable “differentiated fracturing scale window” tailored to coal petrophysical classes and wellbore trajectory positions was defined. Subsequently, a machine learning-assisted geology-engineering closed-loop optimization methodology was established, using tracer data as a dynamic feedback bridge to iteratively refine fracturing designs. This research provides a reliable technical approach and practical template for enhancing single-well productivity and recovery efficiency in deep unconventional gas reservoirs. Full article

Background/Objectives: Small-cell prostate cancer (SCPC) is a rare, aggressive variant of prostate cancer with poor prognosis, arising “de novo” or through lineage plasticity from conventional adenocarcinoma under androgen receptor-targeted therapies. Characterized by low PSA levels despite high tumor burden and visceral metastases, SCPC poses diagnostic challenges with conventional and PSMA-targeted imaging due to variable tracer uptake. This narrative review aims to evaluate the role of PET/CT tracers in clinical and preclinical settings for SCPC diagnosis, staging, and management. Methods: A systematic literature search was conducted on PubMed and Scopus up to December 2025 using terms “PET OR positron emission tomography AND prostate OR prostatic AND small-cell NOT non-small-cell”. Eight studies (five clinical, three preclinical) on the role of PET/CT imaging in SCPC were included and analyzed for study design, population, tracers, and findings, with comparative evaluation of diagnostic performance across PET tracers. Results: Clinical studies showed that ¹¹C-choline detects progression at low PSA but misses SCPC; ¹⁸F-FDG exhibited a high SUVmax value for distinguishing SCPC from adenocarcinomas with neuroendocrine differentiation, predicting poor survival; ⁶⁸Ga-DOTATATE identified NEPC/SCPC with promising prognostic/therapeutic value for selected cases. Preclinical models evaluated ⁸⁹Zr-tracers targeting DLL3 or CDCP1 (an antigen expressed in aggressive neuroendocrine tumours) and ¹⁸F-BnTP (a target of mitochondrial activity) in SCPC subtypes, focusing on translational imaging. Conclusions: From this review, although still based on limited literature evidence and mostly derived from retrospective and small SCPC sub-cohorts,¹⁸F-FDG PET/CT currently appears as the most reliable tracer for SCPC, aiding tumor detection and prognostication when PSMA/choline imaging fails. In the preclinical setting, DLL3/CDCP1-targeted agents emerge as promising theranostics tools. Multimodal imaging approach and prospective trials are needed for standardization and patient-based SCPC management. Full article

This scoping review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines. It summarizes advances in fibroblast activation protein inhibitor (FAPI) positron emission tomography (PET) for oncologic and fibroinflammatory diseases. FAP is expressed broadly on activated mesenchymal cells—including cancer-associated fibroblasts (CAFs) and myofibroblasts within desmoplastic tumor stroma, FAP-positive tumor cells in selected sarcomas, and activated fibroblasts in chronic fibroinflammatory disorders such as rheumatoid arthritis, Crohn’s disease, and organ fibrosis. By targeting these activated fibroblasts, [⁶⁸Ga]- and [¹⁸F]-labeled FAPI tracers provide high tumor-to-background contrast, particularly in desmoplastic and stromal-rich cancers. Compared with [¹⁸F]FDG, FAPI PET demonstrates superior lesion conspicuity in selected malignancies and enables a streamlined, non-fasting imaging workflow. Beyond oncology, FAPI PET is emerging as a promising tool for assessing cardiac fibrosis, pulmonary inflammation, and autoimmune conditions characterized by fibroblast activation. A systematic literature search of PubMed and Scopus was performed for peer-reviewed publications from 1 January 2018 to 28 February 2026. Inclusion criteria encompassed original studies, systematic reviews, meta-analyses, clinical guidelines, case series, and case reports reporting on FAPI-targeted PET in human subjects or translational models, published in English. After screening, 256 sources met the eligibility criteria and are included. The development of standardized SNMMI/EANM imaging protocols, along with ongoing multicenter trials and the first prospective phase 2 clinical trial of ⁶⁸Ga-FAPI-46 PET with histopathological confirmation, now supports the reproducible implementation of FAPI PET across institutions. FAPI PET demonstrates strong translational potential, largely due to its favorable biodistribution, safety profile, and theranostic flexibility. However, its widespread use in routine clinical practice is contingent upon large-scale clinical validation, structured reader training, and formal regulatory approval. In conclusion, FAPI PET represents a maturing molecular imaging platform targeting activated fibroblasts across oncologic and fibroinflammatory diseases. Its widespread adoption into clinical practice requires large-scale prospective trials, reader training, standardized reporting, and regulatory approval—all of which are now actively underway. Full article

Weak-lensing observations of the Perseus Cluster now indicate a massive sub-halo associated with NGC 1264 and a connecting mass bridge in a system long treated as a benchmark relaxed cool-core cluster. Perseus is also known from X-ray observations to host large-scale gas sloshing and an ancient cold front extending to several hundred kiloparsecs. This paper uses Perseus as a motivation for a narrower population question: do nominally relaxed clusters retain merger history information in residual mass–gas offsets after the obvious signatures of an active merger have faded? A candidate remnant stress–energy interpretation is introduced as one possible covariant language for such a long-lived structure, but the empirical test does not require acceptance of that interpretation. The work then carries out a literature-based pilot test using the cold front outer radius as an independent merger history proxy, published mass–gas or gas tracer offsets for relaxed/cool-core systems, and a separate control cohort of actively dissociative mergers. The resulting three-regime comparison separates young active mergers, relaxed low-offset systems, and relaxed systems with sourced offsets above 5 kpc. For all seven Regime 3 (relaxed, offset $>5$ kpc) systems with vetted cold front/history proxies and sourced mass–gas offset measurements, the directional rank-order association has the predicted sign, ${\rho }_s=0.68$, with $p_{\mathrm{one-sided}}\approx 0.047$ ($p_{\mathrm{two-sided}}\approx 0.094$, $N=7$). The one-sided statistic crosses the conventional $5\%$ threshold. The sample mixes lensing–X-ray centroid offsets, BCG/X-ray peak offsets, and weak-lensing sub-halo separations, and the result is not a decisive population detection: it is a suggestive directional signal in a small heterogeneous archival pilot. Its significance is that a framework-derived directional diagnostic, specified before the sample was assembled, is non-zero in the predicted sense and can now be tested with a homogeneous weak-lensing/X-ray/SZ survey. Full article

The evaluation of therapeutic response is essential in disease monitoring both for disease status and treatment efficacy in inflammatory bowel disease. Here, we focused on the use of positron emission tomography directed towards granzyme B, a serine protease released by activated cytotoxic T cells and natural killer cells, to evaluate the dynamics of therapeutic response in a colitis model. The goal was to explore the use of granzyme B positron emission tomography as a non-invasive biomarker to monitor disease activity and therapeutic response across several treatments in a dextran sulfate sodium-induced colitis model. C57BL/6 interleukin-10 knockout mice were divided into five groups, including a negative control, positive control and three treatment arms (antitumor necrosis factor, prednisolone, and anti-interleukin-23). The negative control group received regular water, while all other groups were induced with colitis via 3% DSS water for 1 week followed by normal water. Treatments were initiated after colitis was induced (anti-TNF antibody, prednisolone, or anti-IL-23 antibody). Positron emission tomography/computed tomography imaging with 68Ga-NOTA-GZP was performed at baseline (after colitis induction, before therapy), and at 1 and 2 weeks after treatment initiation. Histological analyses were also performed at 1 and 2 weeks after treatment initiation. Gzmb expression and histological changes were also assessed with immunofluorescence staining and bulk ribonucleic acid sequencing. Gzmb-targeted PET imaging revealed distinct longitudinal patterns of colonic tracer uptake related to treatment response. In positive control mice with DSS colitis (no treatment), bowel uptake of ⁶⁸Ga-NOTA-GZP increased significantly from baseline to week 2. Anti-TNF treatment reduced granzyme B positron emission tomography uptake significantly at week 2, approaching levels seen in negative controls. In prednisolone-treated mice, ⁶⁸Ga-NOTA-GZP uptake decreased at week 1 but rose significantly by week 2 but still was in normal range. Anti-IL-23 therapy produced a significantly elevated Gzmb PET signal at week 1, followed by a significant decline by week 2 of treatment. The imaging trends were corroborated by tissue analyses and IF staining for Gzmb, which revealed no colonic expression in negative controls and strong Gzmb elevation in positive controls and the prednisolone group but a decreased Gzmb signal in the anti-TNF and late anti-IL-23 groups. Bulk RNA sequencing also supported these findings, with Gzmb gene expression tracking with inflammation severity and NK/T cell abundance and decreasing after effective therapy. Gzmb-targeted PET/CT allows for dynamic and non-invasive assessment of intestinal immune compartment activity and an assessment of therapy in colitis. Gzmb PET was able to detect initial treatment responses of anti-TNF, steroid and anti-IL-23 based on changes in the Gzmb PET signal. This suggests that clinical Gzmb PET imaging may serve as precision imaging for monitoring disease activity with treatment in IBD and help improve patient care by identifying responders and non-responders in real time. Full article

Cardiac positron emission tomography (PET) has undergone substantial development in recent years, moving beyond conventional perfusion imaging toward a multiparametric and increasingly quantitative assessment of cardiovascular disease. This article provides a critical narrative overview of the recent cardiac PET literature, with particular emphasis on studies published over the last five years, and discusses both established tracers and emerging radiopharmaceuticals in contemporary cardiology. Among established applications, 18F-FDG remains relevant for myocardial viability assessment and selected inflammatory indications, although its prognostic and therapeutic implications are less uniform than earlier narratives suggested. For myocardial perfusion imaging, 13N-ammonia and 82Rb PET provide robust assessment of myocardial blood flow and myocardial flow reserve, but their clinical interpretation remains strongly influenced by acquisition protocols, software reproducibility, and methodological standardization. The review also addresses newer tracers, including 68Ga-FAPI for fibroblast activation, 18F-flurpiridaz for high-performance perfusion imaging, 18F-FDOPA for cardiac sympathetic dysfunction, and amyloid-binding PET radiopharmaceuticals for cardiac amyloidosis. Overall, recent evidence supports cardiac PET as a powerful platform for physiologic and molecular imaging, but not as a uniform or methodologically neutral technology. Its current value lies in selective, question-driven clinical use, whereas broader implementation will depend on tracer-specific validation, harmonized quantitative workflows, and clear demonstration of incremental benefit over existing imaging strategies. Full article

Standard 16000-8 of the International Organization for Standardization (ISO 16000-8) specifies the assessment of ventilation performance using age-of-air concepts and tracer gas techniques. Since its publication in 2007, ventilation systems and assessment practices have evolved considerably, driven by increased use of mixed-mode and decentralized ventilation and advances in modeling and measurement technologies. This review examines how ISO 16000-8 can be modernized to harmonize with adjacent ventilation and indoor air quality standards while remaining applicable to contemporary systems and emerging approaches. A structured literature search of Web of Science and Google Scholar identified 76 studies (2007–2026) that engage with ISO 16000-8, age-of-air metrics, or tracer gas-based assessment. The literature was synthesized qualitatively using the framework of Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA), classifying studies into performance assessment, measurement–simulation convergence, and standardization discourse. The synthesis shows that while the conceptual foundations of ISO 16000-8 remain valid, assumptions of homogeneous mixing and steady-state conditions are often violated in real buildings, leading to inconsistent application of age-of-air indicators. Field and laboratory studies under point-source conditions demonstrate reduced ventilation effectiveness of 0.73–0.82 in classrooms and 0.5–1.4 in various indoor environments, instead of ≈1 for perfect mixing. Spatial heterogeneity is also observed in mixed-mode systems, with an efficiency around 0.5. In decentralized and façade-integrated systems, air exchange effectiveness deviates from theoretical expectations, indicating inhomogeneous air renewal and short-circuiting. Field measurements show configuration-dependent discrepancies in air exchange rates (e.g., carbon dioxide vs. perfluorocarbon tracer methods under varying door positions), while wind induces time-varying infiltration. Collectively, the literature demonstrates systematic violations of well-mixed and steady-state assumptions underpinning ISO 16000-8. Fragmentation between ventilation performance standards and indoor air quality regulation limits practical uptake. Emerging experimental, numerical, and data-driven methods complement ISO 16000-8, provided applicability domains and uncertainties are addressed. The review concludes that ISO 16000-8 should be modernized toward a harmonized, performance-based framework integrating diverse ventilation systems and assessment technologies. Full article

The evaluation of sweet spots for infill wells is critical to identifying premium reservoir zones, avoiding fracture hits, and achieving safe, efficient development with maximum production potential. Firstly, considering that geological and engineering factors—such as high fracability and good reservoir quality—are conducive to the formation of complex fracture networks and sufficient gas production after fracturing, quantitative evaluation indicators for fracability and geological properties have been established. Secondly, a classification method for different sweet spot tiers in infill wells was proposed. Lastly, taking the Changning infill pilot wells as an example, for sections not affected by fracture interference, higher sweet spot evaluation scores show a strong correlation with improved predictive performance of tracer-based gas production forecasts. Conversely, in fracture-interfered zones, a discrepancy was observed between the sweet spot evaluation results and actual gas production volumes. The horizontal wellbores were classified into a six-tier system (L1–L6), with tailored fracturing design recommendations provided accordingly. This study offers scientific guidance for the precise evaluation of sweet spots in infill wells and the design of customized staged fracturing, thereby significantly enhancing fracturing effectiveness. Full article

Purpose: Prostate-specific membrane antigen (PSMA) is a well-established molecular target in prostate cancer (PCa). Both radionuclide imaging and near-infrared fluorescence (NIRF) imaging offer high sensitivity for in vivo tumor detection. PSMA-targeted dual-modality probes integrating these two imaging techniques provide complementary preoperative and intraoperative tumor visualization, thereby improving surgical guidance in PCa. In this study, we aimed to develop a novel dual-labeled PSMA probe combining radioactive and fluorescent properties to achieve precise tumor delineation during radical prostatectomy (RP). Methods: A high-affinity PSMA-targeted fluorescent probe (PSMA-DF) was synthesized using solid-phase synthesis. Subsequent radiolabeling with the radionuclide [⁶⁸Ga]Ga yielded the successful generation of a dual-modal PSMA-targeted molecular probe, namely [⁶⁸Ga]Ga-PSMA-DF. The probe was systematically evaluated both in vitro and in vivo, and its safety profile was assessed through acute toxicity testing. Tumor-bearing nude mouse models were established using PSMA-positive 22Rv1 and PSMA-negative PC-3 PCa cell lines. Imaging performance, tumor-targeting specificity, and biodistribution of the probe were comprehensively evaluated using micro-PET imaging, in vivo fluorescence imaging, and biodistribution studies. Results: High-quality and high-purity PSMA-DF was successfully prepared, which exhibited excellent optical properties. Following radiolabeling with [⁶⁸Ga]Ga, a dual-modality radionuclide-fluorescence probe ([⁶⁸Ga]Ga-PSMA-DF) was successfully constructed. In vitro cellular uptake studies demonstrated that 22Rv1 cells had relatively high uptake of the probe, reaching 7.34 ± 0.55 IA%/10⁶ cells at 120 min. In contrast, PC-3 cells and blocked 22Rv1 cells displayed minimal uptake, confirming the specific targeting ability of the probe. In vivo evaluations were conducted on tumor-bearing mice using micro-PET/CT and NIRF imaging. The results revealed that [⁶⁸Ga]Ga-PSMA-DF achieved high specific tumor accumulation in 22Rv1 xenografts, with the peak tumor uptake (SUVmax = 1.748 ± 0.132) and tumor-to-muscle ratio (11.542 ± 1.511) observed at 120 min. Notably, high-contrast fluorescence imaging was also achieved at later time points, yielding a tumor-to-background ratio (TBR) of 6.559 ± 1.415 at 48 h. Notably, ex vivo biodistribution data were consistent with in vivo imaging findings. Conclusions: This preclinical study demonstrates that [⁶⁸Ga]Ga-PSMA-DF exhibits high and specific uptake in PCa models, supporting its potential as a dual-modality tracer for both PET/CT imaging and real-time intraoperative fluorescence guidance during PCa surgery. Full article

The northern Vietnam shelf, particularly the area adjacent to the Red River Fault Zone, is characterized by complex geology and active neotectonics. However, the patterns of degassing and the origins of hydrocarbon gases in this region remain poorly understood. In particular, the potential links between deep-seated fluid migration, fault systems, and gas anomalies in island groundwater systems have not been systematically investigated. This study presents preliminary results of dissolved methane, its homologues (C₂–C₅), helium, hydrogen, and carbon dioxide measurements in groundwater from Co To Island (Northern Vietnam), with the aim of identifying gas origins and assessing structural controls on fluid migration. A significant methane anomaly was discovered, with concentrations reaching up to 10% by volume in the northwestern part of the island. The hydrocarbon homologous series is traced up to pentane (C₅), and CO₂ content is also elevated, with a maximum of 5.4%. The average He concentration of 10.8 ppm significantly exceeds atmospheric equilibrium values, with maximum recorded concentrations of 18 ppm for He and 34.5 ppm for H₂. Stable carbon isotope analysis of methane (δ¹³C-CH₄ values ranging from −50.2‰ to −49.7‰ VPDB), combined with the presence of a complete C₁–C₅ hydrocarbon series and elevated mantle/crustal tracers (He, H₂), indicates a predominantly thermogenic/metamorphogenic origin for the gases, ruling out a purely biogenic source. The spatial distribution of anomalies is structurally controlled, closely associated with the NE-SW trending Co To Fault system and its intersections with subsidiary faults, as corroborated by recent electrical resistivity tomography data. These findings indicate intensive, focused gas leakage from a deep-seated source, likely related to thermogenic/metamorphic processes and active fault-mediated degassing. The results highlight the significant hydrocarbon potential of the region and underscore the critical role of neotectonic activity in controlling fluid migration pathways in island aquifer systems. Full article

This study evaluates the feasibility of continuous indoor pollutant monitoring as an indirect method for assessing extended ventilation performance in residential buildings. This research addresses key limitations of conventional short-term tracer-gas methods, which cannot account for occupant lifestyle, environmental fluctuations, and extended ventilation variability. The study employs a diffusion-based framework to interpret pollutant-concentration equalization across the residential space over extended monitoring periods. We conducted field experiments in an apartment unit equipped with both ducted and non-ducted ventilation systems. Pollutants (PM_2.5, CO₂, HCHO, and aromatic VOCs (BTEX + styrene)) were uniformly emitted. PM_2.5 and CO₂ were continuously monitored at six spatially distributed points using calibrated sensors, while HCHO and aromatic VOCs were quantified by repeated active sampling and laboratory analysis. Under ducted ventilation, average pollutant reduction rates reached 86.8% for PM_2.5, 58.3% for CO₂, and 53.6% for HCHO. Simultaneously, spatial concentration variance decreased by up to 71% within 120 min, indicating strong diffusion-driven equalizations. These results support the feasibility of extended ventilation performance monitoring using continuous pollutant sensing, with implications for IAQ management, energy optimization, and future integration with data-driven predictive models. Full article

B7-H3 (CD276), an immune checkpoint protein, is overexpressed in malignant tumors, while its expression in normal tissues is low, and several B7-H3-targeting therapies are under clinical evaluation. Radionuclide molecular imaging offers a non-invasive method for determining B7-H3 expression levels and may aid in improved patient selection. The feasibility of the use of Affibody molecules for the visualization of B7-H3 was demonstrated earlier. The selection of an approach for routine labeling providing high radiochemical yields and reproducibility is, however, critical for successful clinical translation. The optimal combination of a targeting protein, chelator/linker, and radionuclide should provide high-contrast visualization. In this study, we evaluated an acyclic chelator, tris(3,4-hydroxypyridinone) (THP), for labeling of the Affibody molecule Z_{B7-H3_2} with ⁶⁸Ga and compared its impact on radiolabeling efficiency and targeting properties with the impact of the cyclic chelator 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA). Maleimide derivatives of THP and NOTA were site-specifically coupled to the C-terminal cysteine of Z_{B7-H3_2}. THP-Z_{B7-H3_2} was successfully labeled with ⁶⁸Ga within 5 min of incubation at room temperature, achieving a 100% radiochemical yield. NOTA-Z_B7-H3 required heating at 60 °C for 10 min, and the radiochemical yield was lower. Both radioconjugates exhibited specific binding to B7-H3-expressing cells with similar binding strength, and both tracers demonstrated similar tumor uptake (p > 0.05) in a murine model. The biodistribution was similar, although [⁶⁸Ga]Ga-NOTA-Z_{B7-H3_2} provided slightly but significantly higher tumor-to-liver and tumor-to-spleen ratios. Nonetheless, the advantages of THP include rapid and mild radiolabeling with high efficiency, eliminating the need for heating and a post-purification step, which suggests a potential for streamlined clinical translation of Z_{B7-H3_2}. Full article

Objective: We present the first clinical experience with the BIOGRAPH One next-generation PET/MRI system scanner, evaluating its performance for body and brain imaging in patients across multiple tracers. Methods: A total of 59 patients were scanned on the BIOGRAPH One PET/MRI following standard clinical PET/CT (n = 52) or first-generation PET/MRI (Biograph mMR, n = 7). Scans comprised 30 total body (TB), whole body (WB), or regional scans with [¹⁸F]FDG, and 29 brain scans with either [¹⁸F]FDG (n = 5), [¹⁸F]FE-PE2I (n = 10), [¹⁸F]FET (n = 4), or [⁶⁸Ga]Ga-DOTATOC (n = 10). The PET image quality was visually assessed using a 5-point Likert scale (1 = very good to 5 = very bad) and compared with clinical scans acquired on either a current-generation digital PET/CT or a first-generation PET/MRI system, including evaluation of diagnostic concordance. PET quantification and image noise was compared in brain and WB/TB [¹⁸F]FDG PET scans. Results: PET image quality was rated as good or very good in 93% of scans with a median [inter-quartile range] score of 1.5 [1.5;2]. In 99% of cases, image quality was judged equal to or better than the clinical reference scan (median score 3 [2.5;3]). Diagnostic concordance was observed in 99% of readings. Imaging metrics revealed the anticipated regional bias in brain imaging, while no significant bias was observed in body imaging. Image noise was comparable to that observed with digital PET/CT and demonstrated superiority over first-generation PET/MRI despite potential degradation related to isotope decay in BIOGRAPH One PET/MRI acquisitions scans performed at the end of the imaging workflow. Conclusions: Within the study limitations related to sequential imaging, the BIOGRAPH One PET/MRI scanner demonstrated improved PET sensitivity and workflow potential over its first-generation predecessor, which may allow for broader clinical and research applications. Full article

Background/Objectives: Peptide receptor radionuclide therapy (PRRT) is an established treatment for neuroendocrine tumors (NETs), enabling targeted radiation delivery via radiolabeled peptides. Small cell lung cancer (SCLC) remains a major therapeutic challenge due to its aggressive nature and poor prognosis. Despite advances, relapse rates are high and effective therapies are limited. We previously demonstrated the diagnostic potential of the cholecystokinin-2 receptor (CCK2R)-targeting minigastrin analog [⁶⁸Ga]Ga-DOTA-MGS5 in PET/CT imaging of different NETs. Building on this, we developed and evaluated [¹⁷⁷Lu]Lu-DOTA-MGS5 as a therapeutic PRRT agent. Methods: Preclinical studies investigating the receptor-mediated cellular internalization and intracellular distribution over time in A431 cells with and without CCK2R expression were performed using the fluorescent tracer ATTO-488-MGS5. Short- and long-term cytotoxic effects of [¹⁷⁷Lu]Lu-DOTA-MGS5 were evaluated on the same cell line using trypan blue exclusion and clonogenic survival assays. CCK2R expression was assessed by immunohistochemistry in 42 SCLC tissue specimens. In addition, the first PRRT with [¹⁷⁷Lu]Lu-DOTA-MGS5 was conducted in a patient with extensive disease SCLC (ED-SCLC) after confirming CCK2R-positive uptake in [⁶⁸Ga]Ga-DOTA-MGS5 PET/CT. Results: Rapid binding and internalization into A431-CCK2R cells, with progressive accumulation in intracellular compartments, was observed for ATTO-488-MGS5. Short-term irradiation effects of [¹⁷⁷Lu]Lu-DOTA-MGS5 were comparable for 4 h and 24 h incubation and were between the effects obtained with 2 and 4 Gy of external beam radiotherapy (EBRT). Clonogenic survival of A431-CCK2R cells incubated with increasing activity of [¹⁷⁷Lu]Lu-DOTA-MGS5 decreased in a dose-dependent manner. Immunohistochemistry on SCLC specimens confirmed moderate to high CCK2R expression in 16 out of 42 SCLC samples. In the first patient with SCLC treated with four cycles of [¹⁷⁷Lu]Lu-DOTA-MGS5 with a total activity of 17.2 GBq, an improvement in clinical symptoms was observed. Conclusions: The preclinical and clinical results confirm the feasibility of [¹⁷⁷Lu]Lu-DOTA-MGS5 PRRT in patients with SCLC and support further clinical studies investigating the therapeutic value and clinical applicability of this new CCK2R-targeted theranostic approach in larger patient cohorts. Full article

Recurrent brain tumors—including high-grade gliomas, brain metastases, and aggressive meningiomas—continue to carry a poor prognosis, with high mortality despite therapeutic advances. The aim of this narrative review is to summarize and critically discuss the current evidence on the role of intra-arterial radioligand therapy (RLT) in the treatment of recurrent brain tumors. RLT, a targeted form of radionuclide therapy, has gained increasing attention for its potential theranostic applications in neuro-oncology. A literature search was conducted using PubMed and Scopus, including clinical studies evaluating intra-arterial radioligand delivery in central nervous system tumors. Recent research has explored intra-arterial administration of radioligands targeting somatostatin receptors and prostate-specific membrane antigen (PSMA). Somatostatin receptors are overexpressed in meningiomas, while PSMA is highly expressed in the neovasculature of glioblastomas and brain metastases; both targets can be addressed using lutetium-177 (¹⁷⁷Lu)- or actinium-225 (²²⁵Ac)-labeled radiopharmaceuticals, traditionally delivered intravenously. Available evidence indicates that the intra-arterial route achieves markedly higher radionuclide uptake on ⁶⁸Ga-PSMA-11 and ⁶⁸Ga-DOTATOC PET, as well as increased absorbed doses in dosimetric models. Dosimetric analyses consistently show greater tracer accumulation compared with intravenous administration, without evidence of significant peri-procedural toxicity. Uptake in healthy brain tissue is minimal, and no relevant differences have been reported in liver or salivary gland accumulation between intra-arterial and intravenous RLT. Although based on heterogeneous and limited data, intra-arterial RLT appears to be a promising therapeutic strategy for recurrent brain tumors. Future research should focus on improving radioligand delivery beyond the blood–brain barrier and enhancing effective tumor targeting. Full article